Susannah Marcus-Freeman, OD

The term cataract is derived from the Latin word “catarractes,” which means “waterfall,” as the foamy white opacity of an advanced cataract can be likened to a tempestuous cascade. Cataract is the leading cause of preventable blindness worldwide.^1,2 It is no surprise, therefore, that cataract surgery is the most frequently performed ophthalmic surgical procedure worldwide. Cataract surgeries may reach 30 million annual cases by 2020.³ Given the large number of surgeries being performed, postsurgical complications are not uncommon.

Early postoperative complications from lens exchange (cataract) surgery include increased intraocular pressure (IOP), corneal edema, and corneal wound leakage.⁴ Corneal wound leakage is not uncommon; one study showed that, in 100 cases, almost one-third of incisions leaked.⁵ A 2014 prospective study of 500 postcataract surgery eyes revealed that 48.8% had fluid egress.⁶ Early detection is important so that efforts to restore corneal integrity can immediately be implemented. If not caught early, patients are at risk for developing a cascade of sequelae, including endophthalmitis.

The majority of corneal wound leaks postphacoemulsification are self-limiting and self-sealing. Moderate wound leaks require treatment, as in the following case. Strategies to detect, image, and treat wound leaks are covered in this discussion.

Case Presentation

A 69-year-old male veteran presented with no complaints for a 1-day postoperative visit following right eye phacoemulsification cataract extraction. His best corrected visual acuity in the right eye was 20/40, and his pinhole visual acuity was 20/25+2. On slit-lamp examination, the temporally located main incision appeared well-adhered and was found to be Seidel negative; however, the inferior paracentesis wound was found to be Seidel positive, demonstrating a slow leak. Intraocular pressure (IOP) measured with tonopen was 9 mm Hg.

A bandage soft contact lens was placed on the eye. The patient was instructed not to rub or place any pressure on the eye and to avoid bending and heavy lifting. He was also instructed to continue his postoperative medications (prednisolone 1% every 2 hours and polymyxin B sulfate 4 times daily) in his right eye. A follow-up appointment was scheduled for the next day.

The patient presented for his postoperative day-2 visit with a best corrected visual acuity in the right eye of 20/20. He reported no visual problems, no eye pain, and mentioned that he had had a comfortable night sleep. A slit-lamp examination revealed trace diffuse injection in the operative eye, predominantly central Descemet membrane folds, 1+ stromal edema, and a Seidel negative main incision wound. However, the inferior paracentesis wound showed a moderate leak (Seidel positive), and the anterior chamber showed a 1+ cell and flare. Goldmann tonometry revealed an IOP of 5 mm Hg, indicating hypotony.

Anterior segment cube 512 x 128 optical coherence tomography (OCT) was obtained with the bandage contact lens (Figures 1 and 2), and then repeated with the bandage contact lens removed (Figures 3 and 4). OCT imaging confirmed epithelial and endothelial gaping, loss of coaptation, and a localized detachment of the Descemet membrane. The veteran was referred to his surgeon that same day, and 2 limbal vicryl sutures were placed. The patient was instructed to continue prednisolone 1% 4 times daily and polymyxin B sulfate every 2 hours; erythromycin ointment 3 times daily was added to his regimen.

He was scheduled for a follow-up examination 1 week later. At that visit, the wound was no longer leaking and IOP had risen to a preoperative value of 17 mm Hg. The corneal sutures were removed at the 1-month postoperative examination and a follow-up was scheduled for 4 months later. An anterior segment OCT was obtained (Figure 5).

Discussion

In July 1967, Charles Kelman, MD, suggested using a dental ultrasonic tool, normally employed to clean teeth, to fragment the nucleus of the crystalline lens. Dr. Kelman’s first operation using phacoemulsification on a human eye took 3 hours.⁷ As the procedure for cataract removal has been refined, complication rates and surgical times have vastly improved.

Phacoemulsification is the most commonly performed outpatient surgery in the US; about 3 million cases are performed annually. Due to the high volume of cases, adverse events (AEs) are not uncommon. The incidence of complications following phacoemulsification is < 5%; the frequency of severe complications has been estimated at < 0.7%.⁸ Severe complications include endophthalmitis, suprachoroidal hemorrhage, and/or retinal detachment.⁹ Studies have shown a decline in rates of sight-threatening AEs from 1994 to 2006.⁹ A retrospective study of 45,082 veterans from 2005 to 2007 identified that a preoperative disease burden such as diabetes mellitus, chronic pulmonary disease, age-related macular degeneration, and diabetes with ophthalmic manifestations, was positively associated with a greater risk of cataract surgical complications.¹⁰

Complications

The level of a surgeon’s proficiency with phacoemulsification is directly correlated to the number of operations performed; there is a lower complication rate among more experienced surgeons, including those who work in high-volume settings.^11,12 One study identified that the AE rate within 14 days of surgery was 0.8% for surgeons performing 50 to 250 cataract surgeries per year, but only 0.1% for those performing > 1000 cataract surgeries annually.¹²

Potential postoperative lens exchange complications include increased IOP, corneal wound leakage, corneal edema, bullous keratopathy, cystoid macular edema, retinal detachment, and endophthalmitis (Table 1). A corneal wound leak can provide a potential ingress for bacteria, putting the patient at risk for endophthalmitis, perhaps the most devastating complication following cataract surgery.

Endophthalmitis

Endophthalmitis has been reported to occur in .001% to .327% of patients during postoperative care.^5,13-17 Early detection is important to maintain corneal integrity and prevent a cascade of detrimental ocular sequalae including the potential for endophthalmitis. According to Zaida and colleagues, endophthalmitis occurred in fewer than 1 of 1000 consecutive cases.¹⁴ A leaking clear corneal incision wound on the first day postoperatively has been associated with a 44-fold increased risk of endophthalmitis.¹³

Causes of endophthalmitis

In a retrospective case-controlled series of 57 patients with postcataract endophthalmitis, implantation of an intraocular lens with a resultant wound abnormality was thought to be the causative factor in 5%.¹⁷ Another source of endophthalmitis can be the intraocular lens (IOL), which may act as a vector for bacteria. By placing the IOL against the conjunctiva or exposing it to the theater air during surgery, bacteria can be introduced prior to implantation.¹⁷ Immunosuppressive treatment is the only patient antecedent factor that can be considered a predictor for endopthalmitis.¹⁷

The internal corneal seal is IOP dependent, and postoperative ocular hypotony may cause a seemingly watertight wound to leak. Taban and colleagues used anterior segment OCT to image numerous self-sealing incisions. They found that the corneal incision wound more tightly seals at higher IOPs. Additionally, more perpendicular (larger angle) incisions seal better at a lower IOP while less perpendicular (smaller angle) incisions seal better at a higher IOP (Figure 6).¹⁸

Incision Placement

Studies have shown that the main incision site is more clinically competent than is the side port incision site, as in our case study.¹⁹ Side-port incisions have a 1- or 2-plane architectural profile in contrast to the 3-plane profile typical of a main incision.¹⁹ Recent advances including the conversion to clear-corneal incisions of diminishing size, techniques used for wound construction, phacoemulsification machine design, and small-incision IOLs, should further reduce the prevalence and complications of wound compromise.²⁰

Seidel Testing

Seidel testing is the most common method to evaluate corneal wound integrity and identify leaks. A drop of topical anesthetic is instilled in the eye and then a fluorescein strip (not fluorescein sodium and benoxinate hydrochloride ophthalmic solution, which may become less sterile since it has a multiuse container) is applied to the superior conjunctiva. The clinician then looks for evidence of fluid egress using the cobalt blue filter. The patient is instructed to blink once. Fluid egress appears as a black stream as the fluorescein dye becomes diluted by aqueous humor escaping the nonintact wound and the appearance of bright green dye surrounds the leak site. The term Seidel positive indicates a leak. An estimate should be made of the rate and volume of fluid exiting the wound.

Gonioscopy

Gonioscopy can be used to evaluate the postsurgical incision, more specifically for identification and management of internal incision wound gape. On gonioscopy, internal wound gape appears as an elongated oval opening resembling a fish mouth. If internal incision wound gape is identified gonioscopically before surgery is complete, the leak can be managed intraoperatively. The surgeon can irrigate along the length of the incision to remove cortical fragments or viscoelastic that may cause internal wound gaping. If unsuccessful, rapidly deepening the anterior chamber with balanced salt solution through the paracentesis incision may be employed. These methods may improve wound stability, reduce risk of postoperative hyphema, lower the incidence of endophthalmitis, and lessen the likelihood of late against-the-rule drift.²¹

Anterior Segment Optical Coherence Tomography

Instances when Seidel testing was negative despite actual wound gaping have been described.^22,23 Anterior segment OCT is useful to evaluate incision architecture. A 2007 United Kingdom study investigated the corneal architecture in the immediate postoperative period following phacoemulsification using anterior segment OCT. This study showed the benefits of identifying architectural features such as epithelial gaping, endothelial gaping, stripping of Descemet membrane, and loss of coaptation. These features were found to be more common at low IOP and could represent a significant risk factor for endophthalmitis.²⁴ Another study published by Behrens and colleagues indicated that a localized detachment of Descemet membrane may be more common than observed with slit-lamp (Figure 7). Corneal gaping, especially if along the entire length of the surgical wound, may lead to inadvertent bacterial access into the anterior chamber.²⁵ 

Anterior segment OCT imaging was first described by Izatt and colleagues in 1994.²⁶ Unlike posterior segment OCT, anterior segment OCT requires a greater depth of field and higher energy levels as images are commonly distorted by refraction at boundaries where the refractive index changes. Longer infrared wavelengths improve the penetration through tissues that scatter light, such as the sclera and limbus, which allows visualization, for example, of the iridocorneal angle.^27,28

Two main scan patterns are used for anterior segment OCT: 512 x 128 cube scan (4-mm width x 4-mm length) and 5-line raster (3-mm length) with adjustable rotation and spacing. A recent software update allows measurement of corneal thickness, visualization of anterior chamber angle structures along with topographic analysis, anterior and posterior elevation maps of the cornea, and reliable pachymetric maps.^29,30 The anterior segment cube acquires a series of 128 horizontal scan lines each composed of 512 A-scans. These high-definition scans acquire vertical and horizontal directions composed of 1024 A-scans each. This cube may be used to measure corneal thickness and visualize corneal architecture, creating a 3-D image of the data (Figure 8). The anterior segment 5-line raster scans through 5 parallel lines of equal length to view high-resolution images of the anterior chamber angle and cornea. Each line, fixed at 3-mm in length, is composed of 4096 A-scans.³¹ Anterior segment cube OCT allows identification of subtle variations in incision architecture at different locations across the width of the OCT image.

Bandage Soft Contact Lens

Upon reviewing the anterior segment OCT images of our patient with the bandage contact lens in place, it was evident that the adherent ocular bandage was protecting the incision. A tighter fitting bandage contact lens is ideal and adheres firmly to any area of epithelial damage and epithelial gaping to help seal the incision, protecting the wound and improving structural integrity. The bandage contact lens is gradually replaced by new cells via re-epithelialization; thus, it behaves as an adjunct to natural wound healing. A bandage contact lens also improves patient comfort.

It is hypothesized that a bandage contact lens improves the structural integrity of the incision site and helps prevent leaking, hypotony, and minor wound leaks. One study revealed a statistically significant lower IOP in nonbandage contact lens patients by an average of 6 mm Hg (mean [SD] 13.4 mm Hg [5.3]; range, 5 - 23 mm Hg) vs patients with a bandage contact lens (mean [SD] 19.4 mm Hg [5.9]; range, 11 - 29 mm Hg) in the immediate postoperative period.³² The authors suggested that the bandage contact lens may prevent microleaks, resulting in a higher IOP.

Aqueous Suppressants

Aqueous suppressants are a great option when IOP is abnormally elevated by decreasing the IOP and allowing the cornea to heal and self-seal.Effective aqueous suppressants are β blockers and carbonic anhydrase inhibitors.

After phacoemulsification ocular hypotony (< 6 mm Hg) occurs most commonly due to wound leakage or excessive intraocular inflammation. However, with the presence of corneal wound leakage and ocular hypotony, aqueous suppressants are not the best option.

Further Management of Wound Leaks

Management of a postoperative wound leak will vary based on severity. The majority of mild leaks are self-sealing. Anterior segment OCT helps the clinician to identify microleaks in an otherwise Seidel negative eye. If wound leakage is moderate with a formed anterior chamber, the use of a bandage contact lens is a good option, as can be the prescription of aqueous suppressants, depending on IOP.³³

If the anterior chamber is flat, iris prolapse is apparent, or extremely low IOP exists, the patient needs to be referred to the surgeon. Current standard of care directs the surgeon to use sutures to further manage corneal wound leak. However, several studies have recognized the increased risk of suture-related complications, such as induced astigmatism, corneal opacities, incomplete wound closure, and corneal neovascularization.^6,34-38 Other wound closure options include polyethylene glycol-based products, corneal welding, cyanoacrylate, or fibrin (Table 2).³⁹ Traditionally nylon sutures have been used for clear corneal incision wound closure. However, tissue adhesives are gaining popularity as a substitute for sutures in wound closure.⁴⁰

Cyanoacrylate

Numerous studies have been published on the efficacy of cyanoacrylate as a substitute for sutures, specifically in clear corneal incisions. AEs of cyanoacrylate include a transient foreign-body sensation and diffuse or focal bulbar conjunctival hyperemia.^41,42 Shigemitsu and Majima found that fibrin and cyanoacrylate glue had tensile strength similar to sutures when used in cataract surgery.39 
Polyethylene glycol-based products, also used in artificial tears and contact lens materials, may also help seal wound leaks. Another agent is ReSure (Ocular Therapeutix, Bedford, MA), an FDA-approved synthetic, polyethylene glycol hydrogel sealant that is 90% water after polymerization. ReSure has been shown to be safe and effective in sealing cataract surgical clear corneal incisions.^6,43 ReSure takes about 20 seconds to prepare, and placement is aided by the use of a blue dye that dissipates within hours. This hydrogel will gradually slough off in the tears once the tissue has fully regenerated; there is no need to remove the sealant.⁴⁴

Rossi and colleagues evaluated the efficacy of corneal welding to close wounds after cataract surgery. The technique involves laser-assisted closure of the corneal wound(s) by a diode laser that welds the stroma.⁴⁵ Corneal welding takes seconds to achieve good closure without significant astigmatism or inflammation; however very careful application of the light absorbing dyes is required as they are toxic if allowed to enter the anterior chamber.^45-47

Conclusion

Optometrists may be called to manage patients during both the preoperative and postoperative phases of cataract surgical care. Those who participate in postoperative care should carefully evaluate for the presence of wound leak or wound gape as a potential complication. The OCT may be employed to evaluate patients suspected of having these leaks or gapes. Proficiency in the interpretation of OCT results and more traditional evaluation methods allows for successful detection of wound leaks or gapes. The timely diagnosis and treatment of postoperative wound leaks allow for the best possible outcomes for cataract surgery patients.

The term cataract is derived from the Latin word “catarractes,” which means “waterfall,” as the foamy white opacity of an advanced cataract can be likened to a tempestuous cascade. Cataract is the leading cause of preventable blindness worldwide.^1,2 It is no surprise, therefore, that cataract surgery is the most frequently performed ophthalmic surgical procedure worldwide. Cataract surgeries may reach 30 million annual cases by 2020.³ Given the large number of surgeries being performed, postsurgical complications are not uncommon.

Early postoperative complications from lens exchange (cataract) surgery include increased intraocular pressure (IOP), corneal edema, and corneal wound leakage.⁴ Corneal wound leakage is not uncommon; one study showed that, in 100 cases, almost one-third of incisions leaked.⁵ A 2014 prospective study of 500 postcataract surgery eyes revealed that 48.8% had fluid egress.⁶ Early detection is important so that efforts to restore corneal integrity can immediately be implemented. If not caught early, patients are at risk for developing a cascade of sequelae, including endophthalmitis.

The majority of corneal wound leaks postphacoemulsification are self-limiting and self-sealing. Moderate wound leaks require treatment, as in the following case. Strategies to detect, image, and treat wound leaks are covered in this discussion.

Case Presentation

A 69-year-old male veteran presented with no complaints for a 1-day postoperative visit following right eye phacoemulsification cataract extraction. His best corrected visual acuity in the right eye was 20/40, and his pinhole visual acuity was 20/25+2. On slit-lamp examination, the temporally located main incision appeared well-adhered and was found to be Seidel negative; however, the inferior paracentesis wound was found to be Seidel positive, demonstrating a slow leak. Intraocular pressure (IOP) measured with tonopen was 9 mm Hg.

A bandage soft contact lens was placed on the eye. The patient was instructed not to rub or place any pressure on the eye and to avoid bending and heavy lifting. He was also instructed to continue his postoperative medications (prednisolone 1% every 2 hours and polymyxin B sulfate 4 times daily) in his right eye. A follow-up appointment was scheduled for the next day.

The patient presented for his postoperative day-2 visit with a best corrected visual acuity in the right eye of 20/20. He reported no visual problems, no eye pain, and mentioned that he had had a comfortable night sleep. A slit-lamp examination revealed trace diffuse injection in the operative eye, predominantly central Descemet membrane folds, 1+ stromal edema, and a Seidel negative main incision wound. However, the inferior paracentesis wound showed a moderate leak (Seidel positive), and the anterior chamber showed a 1+ cell and flare. Goldmann tonometry revealed an IOP of 5 mm Hg, indicating hypotony.

Anterior segment cube 512 x 128 optical coherence tomography (OCT) was obtained with the bandage contact lens (Figures 1 and 2), and then repeated with the bandage contact lens removed (Figures 3 and 4). OCT imaging confirmed epithelial and endothelial gaping, loss of coaptation, and a localized detachment of the Descemet membrane. The veteran was referred to his surgeon that same day, and 2 limbal vicryl sutures were placed. The patient was instructed to continue prednisolone 1% 4 times daily and polymyxin B sulfate every 2 hours; erythromycin ointment 3 times daily was added to his regimen.

He was scheduled for a follow-up examination 1 week later. At that visit, the wound was no longer leaking and IOP had risen to a preoperative value of 17 mm Hg. The corneal sutures were removed at the 1-month postoperative examination and a follow-up was scheduled for 4 months later. An anterior segment OCT was obtained (Figure 5).

Discussion

In July 1967, Charles Kelman, MD, suggested using a dental ultrasonic tool, normally employed to clean teeth, to fragment the nucleus of the crystalline lens. Dr. Kelman’s first operation using phacoemulsification on a human eye took 3 hours.⁷ As the procedure for cataract removal has been refined, complication rates and surgical times have vastly improved.

Phacoemulsification is the most commonly performed outpatient surgery in the US; about 3 million cases are performed annually. Due to the high volume of cases, adverse events (AEs) are not uncommon. The incidence of complications following phacoemulsification is < 5%; the frequency of severe complications has been estimated at < 0.7%.⁸ Severe complications include endophthalmitis, suprachoroidal hemorrhage, and/or retinal detachment.⁹ Studies have shown a decline in rates of sight-threatening AEs from 1994 to 2006.⁹ A retrospective study of 45,082 veterans from 2005 to 2007 identified that a preoperative disease burden such as diabetes mellitus, chronic pulmonary disease, age-related macular degeneration, and diabetes with ophthalmic manifestations, was positively associated with a greater risk of cataract surgical complications.¹⁰

Complications

The level of a surgeon’s proficiency with phacoemulsification is directly correlated to the number of operations performed; there is a lower complication rate among more experienced surgeons, including those who work in high-volume settings.^11,12 One study identified that the AE rate within 14 days of surgery was 0.8% for surgeons performing 50 to 250 cataract surgeries per year, but only 0.1% for those performing > 1000 cataract surgeries annually.¹²

Potential postoperative lens exchange complications include increased IOP, corneal wound leakage, corneal edema, bullous keratopathy, cystoid macular edema, retinal detachment, and endophthalmitis (Table 1). A corneal wound leak can provide a potential ingress for bacteria, putting the patient at risk for endophthalmitis, perhaps the most devastating complication following cataract surgery.

Endophthalmitis

Endophthalmitis has been reported to occur in .001% to .327% of patients during postoperative care.^5,13-17 Early detection is important to maintain corneal integrity and prevent a cascade of detrimental ocular sequalae including the potential for endophthalmitis. According to Zaida and colleagues, endophthalmitis occurred in fewer than 1 of 1000 consecutive cases.¹⁴ A leaking clear corneal incision wound on the first day postoperatively has been associated with a 44-fold increased risk of endophthalmitis.¹³

Causes of endophthalmitis

In a retrospective case-controlled series of 57 patients with postcataract endophthalmitis, implantation of an intraocular lens with a resultant wound abnormality was thought to be the causative factor in 5%.¹⁷ Another source of endophthalmitis can be the intraocular lens (IOL), which may act as a vector for bacteria. By placing the IOL against the conjunctiva or exposing it to the theater air during surgery, bacteria can be introduced prior to implantation.¹⁷ Immunosuppressive treatment is the only patient antecedent factor that can be considered a predictor for endopthalmitis.¹⁷

The internal corneal seal is IOP dependent, and postoperative ocular hypotony may cause a seemingly watertight wound to leak. Taban and colleagues used anterior segment OCT to image numerous self-sealing incisions. They found that the corneal incision wound more tightly seals at higher IOPs. Additionally, more perpendicular (larger angle) incisions seal better at a lower IOP while less perpendicular (smaller angle) incisions seal better at a higher IOP (Figure 6).¹⁸

Incision Placement

Studies have shown that the main incision site is more clinically competent than is the side port incision site, as in our case study.¹⁹ Side-port incisions have a 1- or 2-plane architectural profile in contrast to the 3-plane profile typical of a main incision.¹⁹ Recent advances including the conversion to clear-corneal incisions of diminishing size, techniques used for wound construction, phacoemulsification machine design, and small-incision IOLs, should further reduce the prevalence and complications of wound compromise.²⁰

Seidel Testing

Seidel testing is the most common method to evaluate corneal wound integrity and identify leaks. A drop of topical anesthetic is instilled in the eye and then a fluorescein strip (not fluorescein sodium and benoxinate hydrochloride ophthalmic solution, which may become less sterile since it has a multiuse container) is applied to the superior conjunctiva. The clinician then looks for evidence of fluid egress using the cobalt blue filter. The patient is instructed to blink once. Fluid egress appears as a black stream as the fluorescein dye becomes diluted by aqueous humor escaping the nonintact wound and the appearance of bright green dye surrounds the leak site. The term Seidel positive indicates a leak. An estimate should be made of the rate and volume of fluid exiting the wound.

Gonioscopy

Gonioscopy can be used to evaluate the postsurgical incision, more specifically for identification and management of internal incision wound gape. On gonioscopy, internal wound gape appears as an elongated oval opening resembling a fish mouth. If internal incision wound gape is identified gonioscopically before surgery is complete, the leak can be managed intraoperatively. The surgeon can irrigate along the length of the incision to remove cortical fragments or viscoelastic that may cause internal wound gaping. If unsuccessful, rapidly deepening the anterior chamber with balanced salt solution through the paracentesis incision may be employed. These methods may improve wound stability, reduce risk of postoperative hyphema, lower the incidence of endophthalmitis, and lessen the likelihood of late against-the-rule drift.²¹

Anterior Segment Optical Coherence Tomography

Instances when Seidel testing was negative despite actual wound gaping have been described.^22,23 Anterior segment OCT is useful to evaluate incision architecture. A 2007 United Kingdom study investigated the corneal architecture in the immediate postoperative period following phacoemulsification using anterior segment OCT. This study showed the benefits of identifying architectural features such as epithelial gaping, endothelial gaping, stripping of Descemet membrane, and loss of coaptation. These features were found to be more common at low IOP and could represent a significant risk factor for endophthalmitis.²⁴ Another study published by Behrens and colleagues indicated that a localized detachment of Descemet membrane may be more common than observed with slit-lamp (Figure 7). Corneal gaping, especially if along the entire length of the surgical wound, may lead to inadvertent bacterial access into the anterior chamber.²⁵ 

Anterior segment OCT imaging was first described by Izatt and colleagues in 1994.²⁶ Unlike posterior segment OCT, anterior segment OCT requires a greater depth of field and higher energy levels as images are commonly distorted by refraction at boundaries where the refractive index changes. Longer infrared wavelengths improve the penetration through tissues that scatter light, such as the sclera and limbus, which allows visualization, for example, of the iridocorneal angle.^27,28

Two main scan patterns are used for anterior segment OCT: 512 x 128 cube scan (4-mm width x 4-mm length) and 5-line raster (3-mm length) with adjustable rotation and spacing. A recent software update allows measurement of corneal thickness, visualization of anterior chamber angle structures along with topographic analysis, anterior and posterior elevation maps of the cornea, and reliable pachymetric maps.^29,30 The anterior segment cube acquires a series of 128 horizontal scan lines each composed of 512 A-scans. These high-definition scans acquire vertical and horizontal directions composed of 1024 A-scans each. This cube may be used to measure corneal thickness and visualize corneal architecture, creating a 3-D image of the data (Figure 8). The anterior segment 5-line raster scans through 5 parallel lines of equal length to view high-resolution images of the anterior chamber angle and cornea. Each line, fixed at 3-mm in length, is composed of 4096 A-scans.³¹ Anterior segment cube OCT allows identification of subtle variations in incision architecture at different locations across the width of the OCT image.

Bandage Soft Contact Lens

Upon reviewing the anterior segment OCT images of our patient with the bandage contact lens in place, it was evident that the adherent ocular bandage was protecting the incision. A tighter fitting bandage contact lens is ideal and adheres firmly to any area of epithelial damage and epithelial gaping to help seal the incision, protecting the wound and improving structural integrity. The bandage contact lens is gradually replaced by new cells via re-epithelialization; thus, it behaves as an adjunct to natural wound healing. A bandage contact lens also improves patient comfort.

It is hypothesized that a bandage contact lens improves the structural integrity of the incision site and helps prevent leaking, hypotony, and minor wound leaks. One study revealed a statistically significant lower IOP in nonbandage contact lens patients by an average of 6 mm Hg (mean [SD] 13.4 mm Hg [5.3]; range, 5 - 23 mm Hg) vs patients with a bandage contact lens (mean [SD] 19.4 mm Hg [5.9]; range, 11 - 29 mm Hg) in the immediate postoperative period.³² The authors suggested that the bandage contact lens may prevent microleaks, resulting in a higher IOP.

Aqueous Suppressants

Aqueous suppressants are a great option when IOP is abnormally elevated by decreasing the IOP and allowing the cornea to heal and self-seal.Effective aqueous suppressants are β blockers and carbonic anhydrase inhibitors.

After phacoemulsification ocular hypotony (< 6 mm Hg) occurs most commonly due to wound leakage or excessive intraocular inflammation. However, with the presence of corneal wound leakage and ocular hypotony, aqueous suppressants are not the best option.

Further Management of Wound Leaks

Management of a postoperative wound leak will vary based on severity. The majority of mild leaks are self-sealing. Anterior segment OCT helps the clinician to identify microleaks in an otherwise Seidel negative eye. If wound leakage is moderate with a formed anterior chamber, the use of a bandage contact lens is a good option, as can be the prescription of aqueous suppressants, depending on IOP.³³

If the anterior chamber is flat, iris prolapse is apparent, or extremely low IOP exists, the patient needs to be referred to the surgeon. Current standard of care directs the surgeon to use sutures to further manage corneal wound leak. However, several studies have recognized the increased risk of suture-related complications, such as induced astigmatism, corneal opacities, incomplete wound closure, and corneal neovascularization.^6,34-38 Other wound closure options include polyethylene glycol-based products, corneal welding, cyanoacrylate, or fibrin (Table 2).³⁹ Traditionally nylon sutures have been used for clear corneal incision wound closure. However, tissue adhesives are gaining popularity as a substitute for sutures in wound closure.⁴⁰

Cyanoacrylate

Numerous studies have been published on the efficacy of cyanoacrylate as a substitute for sutures, specifically in clear corneal incisions. AEs of cyanoacrylate include a transient foreign-body sensation and diffuse or focal bulbar conjunctival hyperemia.^41,42 Shigemitsu and Majima found that fibrin and cyanoacrylate glue had tensile strength similar to sutures when used in cataract surgery.39 
Polyethylene glycol-based products, also used in artificial tears and contact lens materials, may also help seal wound leaks. Another agent is ReSure (Ocular Therapeutix, Bedford, MA), an FDA-approved synthetic, polyethylene glycol hydrogel sealant that is 90% water after polymerization. ReSure has been shown to be safe and effective in sealing cataract surgical clear corneal incisions.^6,43 ReSure takes about 20 seconds to prepare, and placement is aided by the use of a blue dye that dissipates within hours. This hydrogel will gradually slough off in the tears once the tissue has fully regenerated; there is no need to remove the sealant.⁴⁴

Rossi and colleagues evaluated the efficacy of corneal welding to close wounds after cataract surgery. The technique involves laser-assisted closure of the corneal wound(s) by a diode laser that welds the stroma.⁴⁵ Corneal welding takes seconds to achieve good closure without significant astigmatism or inflammation; however very careful application of the light absorbing dyes is required as they are toxic if allowed to enter the anterior chamber.^45-47

Conclusion

Optometrists may be called to manage patients during both the preoperative and postoperative phases of cataract surgical care. Those who participate in postoperative care should carefully evaluate for the presence of wound leak or wound gape as a potential complication. The OCT may be employed to evaluate patients suspected of having these leaks or gapes. Proficiency in the interpretation of OCT results and more traditional evaluation methods allows for successful detection of wound leaks or gapes. The timely diagnosis and treatment of postoperative wound leaks allow for the best possible outcomes for cataract surgery patients.

The term cataract is derived from the Latin word “catarractes,” which means “waterfall,” as the foamy white opacity of an advanced cataract can be likened to a tempestuous cascade. Cataract is the leading cause of preventable blindness worldwide.^1,2 It is no surprise, therefore, that cataract surgery is the most frequently performed ophthalmic surgical procedure worldwide. Cataract surgeries may reach 30 million annual cases by 2020.³ Given the large number of surgeries being performed, postsurgical complications are not uncommon.

Early postoperative complications from lens exchange (cataract) surgery include increased intraocular pressure (IOP), corneal edema, and corneal wound leakage.⁴ Corneal wound leakage is not uncommon; one study showed that, in 100 cases, almost one-third of incisions leaked.⁵ A 2014 prospective study of 500 postcataract surgery eyes revealed that 48.8% had fluid egress.⁶ Early detection is important so that efforts to restore corneal integrity can immediately be implemented. If not caught early, patients are at risk for developing a cascade of sequelae, including endophthalmitis.

The majority of corneal wound leaks postphacoemulsification are self-limiting and self-sealing. Moderate wound leaks require treatment, as in the following case. Strategies to detect, image, and treat wound leaks are covered in this discussion.

Case Presentation

A 69-year-old male veteran presented with no complaints for a 1-day postoperative visit following right eye phacoemulsification cataract extraction. His best corrected visual acuity in the right eye was 20/40, and his pinhole visual acuity was 20/25+2. On slit-lamp examination, the temporally located main incision appeared well-adhered and was found to be Seidel negative; however, the inferior paracentesis wound was found to be Seidel positive, demonstrating a slow leak. Intraocular pressure (IOP) measured with tonopen was 9 mm Hg.

A bandage soft contact lens was placed on the eye. The patient was instructed not to rub or place any pressure on the eye and to avoid bending and heavy lifting. He was also instructed to continue his postoperative medications (prednisolone 1% every 2 hours and polymyxin B sulfate 4 times daily) in his right eye. A follow-up appointment was scheduled for the next day.

The patient presented for his postoperative day-2 visit with a best corrected visual acuity in the right eye of 20/20. He reported no visual problems, no eye pain, and mentioned that he had had a comfortable night sleep. A slit-lamp examination revealed trace diffuse injection in the operative eye, predominantly central Descemet membrane folds, 1+ stromal edema, and a Seidel negative main incision wound. However, the inferior paracentesis wound showed a moderate leak (Seidel positive), and the anterior chamber showed a 1+ cell and flare. Goldmann tonometry revealed an IOP of 5 mm Hg, indicating hypotony.

Anterior segment cube 512 x 128 optical coherence tomography (OCT) was obtained with the bandage contact lens (Figures 1 and 2), and then repeated with the bandage contact lens removed (Figures 3 and 4). OCT imaging confirmed epithelial and endothelial gaping, loss of coaptation, and a localized detachment of the Descemet membrane. The veteran was referred to his surgeon that same day, and 2 limbal vicryl sutures were placed. The patient was instructed to continue prednisolone 1% 4 times daily and polymyxin B sulfate every 2 hours; erythromycin ointment 3 times daily was added to his regimen.

He was scheduled for a follow-up examination 1 week later. At that visit, the wound was no longer leaking and IOP had risen to a preoperative value of 17 mm Hg. The corneal sutures were removed at the 1-month postoperative examination and a follow-up was scheduled for 4 months later. An anterior segment OCT was obtained (Figure 5).

Discussion

In July 1967, Charles Kelman, MD, suggested using a dental ultrasonic tool, normally employed to clean teeth, to fragment the nucleus of the crystalline lens. Dr. Kelman’s first operation using phacoemulsification on a human eye took 3 hours.⁷ As the procedure for cataract removal has been refined, complication rates and surgical times have vastly improved.

Phacoemulsification is the most commonly performed outpatient surgery in the US; about 3 million cases are performed annually. Due to the high volume of cases, adverse events (AEs) are not uncommon. The incidence of complications following phacoemulsification is < 5%; the frequency of severe complications has been estimated at < 0.7%.⁸ Severe complications include endophthalmitis, suprachoroidal hemorrhage, and/or retinal detachment.⁹ Studies have shown a decline in rates of sight-threatening AEs from 1994 to 2006.⁹ A retrospective study of 45,082 veterans from 2005 to 2007 identified that a preoperative disease burden such as diabetes mellitus, chronic pulmonary disease, age-related macular degeneration, and diabetes with ophthalmic manifestations, was positively associated with a greater risk of cataract surgical complications.¹⁰

Complications

The level of a surgeon’s proficiency with phacoemulsification is directly correlated to the number of operations performed; there is a lower complication rate among more experienced surgeons, including those who work in high-volume settings.^11,12 One study identified that the AE rate within 14 days of surgery was 0.8% for surgeons performing 50 to 250 cataract surgeries per year, but only 0.1% for those performing > 1000 cataract surgeries annually.¹²

Potential postoperative lens exchange complications include increased IOP, corneal wound leakage, corneal edema, bullous keratopathy, cystoid macular edema, retinal detachment, and endophthalmitis (Table 1). A corneal wound leak can provide a potential ingress for bacteria, putting the patient at risk for endophthalmitis, perhaps the most devastating complication following cataract surgery.

Endophthalmitis

Endophthalmitis has been reported to occur in .001% to .327% of patients during postoperative care.^5,13-17 Early detection is important to maintain corneal integrity and prevent a cascade of detrimental ocular sequalae including the potential for endophthalmitis. According to Zaida and colleagues, endophthalmitis occurred in fewer than 1 of 1000 consecutive cases.¹⁴ A leaking clear corneal incision wound on the first day postoperatively has been associated with a 44-fold increased risk of endophthalmitis.¹³

Causes of endophthalmitis

In a retrospective case-controlled series of 57 patients with postcataract endophthalmitis, implantation of an intraocular lens with a resultant wound abnormality was thought to be the causative factor in 5%.¹⁷ Another source of endophthalmitis can be the intraocular lens (IOL), which may act as a vector for bacteria. By placing the IOL against the conjunctiva or exposing it to the theater air during surgery, bacteria can be introduced prior to implantation.¹⁷ Immunosuppressive treatment is the only patient antecedent factor that can be considered a predictor for endopthalmitis.¹⁷

The internal corneal seal is IOP dependent, and postoperative ocular hypotony may cause a seemingly watertight wound to leak. Taban and colleagues used anterior segment OCT to image numerous self-sealing incisions. They found that the corneal incision wound more tightly seals at higher IOPs. Additionally, more perpendicular (larger angle) incisions seal better at a lower IOP while less perpendicular (smaller angle) incisions seal better at a higher IOP (Figure 6).¹⁸

Incision Placement

Studies have shown that the main incision site is more clinically competent than is the side port incision site, as in our case study.¹⁹ Side-port incisions have a 1- or 2-plane architectural profile in contrast to the 3-plane profile typical of a main incision.¹⁹ Recent advances including the conversion to clear-corneal incisions of diminishing size, techniques used for wound construction, phacoemulsification machine design, and small-incision IOLs, should further reduce the prevalence and complications of wound compromise.²⁰

Seidel Testing

Seidel testing is the most common method to evaluate corneal wound integrity and identify leaks. A drop of topical anesthetic is instilled in the eye and then a fluorescein strip (not fluorescein sodium and benoxinate hydrochloride ophthalmic solution, which may become less sterile since it has a multiuse container) is applied to the superior conjunctiva. The clinician then looks for evidence of fluid egress using the cobalt blue filter. The patient is instructed to blink once. Fluid egress appears as a black stream as the fluorescein dye becomes diluted by aqueous humor escaping the nonintact wound and the appearance of bright green dye surrounds the leak site. The term Seidel positive indicates a leak. An estimate should be made of the rate and volume of fluid exiting the wound.

Gonioscopy

Gonioscopy can be used to evaluate the postsurgical incision, more specifically for identification and management of internal incision wound gape. On gonioscopy, internal wound gape appears as an elongated oval opening resembling a fish mouth. If internal incision wound gape is identified gonioscopically before surgery is complete, the leak can be managed intraoperatively. The surgeon can irrigate along the length of the incision to remove cortical fragments or viscoelastic that may cause internal wound gaping. If unsuccessful, rapidly deepening the anterior chamber with balanced salt solution through the paracentesis incision may be employed. These methods may improve wound stability, reduce risk of postoperative hyphema, lower the incidence of endophthalmitis, and lessen the likelihood of late against-the-rule drift.²¹

Anterior Segment Optical Coherence Tomography

Instances when Seidel testing was negative despite actual wound gaping have been described.^22,23 Anterior segment OCT is useful to evaluate incision architecture. A 2007 United Kingdom study investigated the corneal architecture in the immediate postoperative period following phacoemulsification using anterior segment OCT. This study showed the benefits of identifying architectural features such as epithelial gaping, endothelial gaping, stripping of Descemet membrane, and loss of coaptation. These features were found to be more common at low IOP and could represent a significant risk factor for endophthalmitis.²⁴ Another study published by Behrens and colleagues indicated that a localized detachment of Descemet membrane may be more common than observed with slit-lamp (Figure 7). Corneal gaping, especially if along the entire length of the surgical wound, may lead to inadvertent bacterial access into the anterior chamber.²⁵ 

Anterior segment OCT imaging was first described by Izatt and colleagues in 1994.²⁶ Unlike posterior segment OCT, anterior segment OCT requires a greater depth of field and higher energy levels as images are commonly distorted by refraction at boundaries where the refractive index changes. Longer infrared wavelengths improve the penetration through tissues that scatter light, such as the sclera and limbus, which allows visualization, for example, of the iridocorneal angle.^27,28

Two main scan patterns are used for anterior segment OCT: 512 x 128 cube scan (4-mm width x 4-mm length) and 5-line raster (3-mm length) with adjustable rotation and spacing. A recent software update allows measurement of corneal thickness, visualization of anterior chamber angle structures along with topographic analysis, anterior and posterior elevation maps of the cornea, and reliable pachymetric maps.^29,30 The anterior segment cube acquires a series of 128 horizontal scan lines each composed of 512 A-scans. These high-definition scans acquire vertical and horizontal directions composed of 1024 A-scans each. This cube may be used to measure corneal thickness and visualize corneal architecture, creating a 3-D image of the data (Figure 8). The anterior segment 5-line raster scans through 5 parallel lines of equal length to view high-resolution images of the anterior chamber angle and cornea. Each line, fixed at 3-mm in length, is composed of 4096 A-scans.³¹ Anterior segment cube OCT allows identification of subtle variations in incision architecture at different locations across the width of the OCT image.

Bandage Soft Contact Lens

Upon reviewing the anterior segment OCT images of our patient with the bandage contact lens in place, it was evident that the adherent ocular bandage was protecting the incision. A tighter fitting bandage contact lens is ideal and adheres firmly to any area of epithelial damage and epithelial gaping to help seal the incision, protecting the wound and improving structural integrity. The bandage contact lens is gradually replaced by new cells via re-epithelialization; thus, it behaves as an adjunct to natural wound healing. A bandage contact lens also improves patient comfort.

It is hypothesized that a bandage contact lens improves the structural integrity of the incision site and helps prevent leaking, hypotony, and minor wound leaks. One study revealed a statistically significant lower IOP in nonbandage contact lens patients by an average of 6 mm Hg (mean [SD] 13.4 mm Hg [5.3]; range, 5 - 23 mm Hg) vs patients with a bandage contact lens (mean [SD] 19.4 mm Hg [5.9]; range, 11 - 29 mm Hg) in the immediate postoperative period.³² The authors suggested that the bandage contact lens may prevent microleaks, resulting in a higher IOP.

Aqueous Suppressants

Aqueous suppressants are a great option when IOP is abnormally elevated by decreasing the IOP and allowing the cornea to heal and self-seal.Effective aqueous suppressants are β blockers and carbonic anhydrase inhibitors.

After phacoemulsification ocular hypotony (< 6 mm Hg) occurs most commonly due to wound leakage or excessive intraocular inflammation. However, with the presence of corneal wound leakage and ocular hypotony, aqueous suppressants are not the best option.

Further Management of Wound Leaks

Management of a postoperative wound leak will vary based on severity. The majority of mild leaks are self-sealing. Anterior segment OCT helps the clinician to identify microleaks in an otherwise Seidel negative eye. If wound leakage is moderate with a formed anterior chamber, the use of a bandage contact lens is a good option, as can be the prescription of aqueous suppressants, depending on IOP.³³

If the anterior chamber is flat, iris prolapse is apparent, or extremely low IOP exists, the patient needs to be referred to the surgeon. Current standard of care directs the surgeon to use sutures to further manage corneal wound leak. However, several studies have recognized the increased risk of suture-related complications, such as induced astigmatism, corneal opacities, incomplete wound closure, and corneal neovascularization.^6,34-38 Other wound closure options include polyethylene glycol-based products, corneal welding, cyanoacrylate, or fibrin (Table 2).³⁹ Traditionally nylon sutures have been used for clear corneal incision wound closure. However, tissue adhesives are gaining popularity as a substitute for sutures in wound closure.⁴⁰

Cyanoacrylate

Numerous studies have been published on the efficacy of cyanoacrylate as a substitute for sutures, specifically in clear corneal incisions. AEs of cyanoacrylate include a transient foreign-body sensation and diffuse or focal bulbar conjunctival hyperemia.^41,42 Shigemitsu and Majima found that fibrin and cyanoacrylate glue had tensile strength similar to sutures when used in cataract surgery.39 
Polyethylene glycol-based products, also used in artificial tears and contact lens materials, may also help seal wound leaks. Another agent is ReSure (Ocular Therapeutix, Bedford, MA), an FDA-approved synthetic, polyethylene glycol hydrogel sealant that is 90% water after polymerization. ReSure has been shown to be safe and effective in sealing cataract surgical clear corneal incisions.^6,43 ReSure takes about 20 seconds to prepare, and placement is aided by the use of a blue dye that dissipates within hours. This hydrogel will gradually slough off in the tears once the tissue has fully regenerated; there is no need to remove the sealant.⁴⁴

Rossi and colleagues evaluated the efficacy of corneal welding to close wounds after cataract surgery. The technique involves laser-assisted closure of the corneal wound(s) by a diode laser that welds the stroma.⁴⁵ Corneal welding takes seconds to achieve good closure without significant astigmatism or inflammation; however very careful application of the light absorbing dyes is required as they are toxic if allowed to enter the anterior chamber.^45-47

Conclusion

Optometrists may be called to manage patients during both the preoperative and postoperative phases of cataract surgical care. Those who participate in postoperative care should carefully evaluate for the presence of wound leak or wound gape as a potential complication. The OCT may be employed to evaluate patients suspected of having these leaks or gapes. Proficiency in the interpretation of OCT results and more traditional evaluation methods allows for successful detection of wound leaks or gapes. The timely diagnosis and treatment of postoperative wound leaks allow for the best possible outcomes for cataract surgery patients.

Phenylephrine, a sympathomimetic drug, is commonly used in eye exams to dilate the pupil of the eye and to differentiate scleritis from episcleritis. Common adverse effects (AEs) of phenylephrine include subjective burning, stinging with lacrimation, rebound hyperemia, and liberation of iris pigment into the anterior chamber. Less common, systemic AEs include tachycardia and elevation of systemic blood pressure. Although instances of allergic reactions are rare, phenylephrine has been reported to cause contact dermatitis, blepharoconjunctivitis, and as in this case, keratoconjunctivitis.

Case Report

An 83-year-old white male presented for a red eye evaluation 2 days after having undergone a comprehensive eye exam with dilation at the Malcom Randall VAMC clinic in Gainesville, Florida. The patient reported onset of blurred vision, which he described as looking through a fog. He further compared the feeling to pins sticking in his eyes. The patient noted he had experienced similar symptoms on a few other occasions following eye exams. At the most recent eye exam, proparacaine and fluorescein had been used for tonometry, and phenylephrine 2.5% and tropicamide 0.5% had been used for pupillary dilation.

The patient’s best-corrected visual acuity was counting fingers at 2 feet in the right eye (OD) and left eye (OS). The best-corrected visual acuity 2 days prior had been 20/20 OD and OS. Pupils and extraocular motilities were unremarkable. Intraocular pressures were not obtained due to concern for a possible adverse reaction to proparacaine.

Slit-lamp evaluation revealed the lids to be lax, erythematous, and edematous in both eyes (Figure 1).

The initial diagnosis was acute chemical conjunctivitis most likely due to an AE to proparacaine. The plan was to start the patient on antibiotic eye drops qid OU, prednisolone qid OU, and artificial tears every hour OU. The patient was scheduled to return to clinic 4 days later for an anterior segment follow-up.

At the follow-up visit, the patient reported significant visual improvement. His best-corrected visual acuity was 20/40-2 without improvement on pinhole OD and 20/50-2 with improvement to 20/30+ on pinhole OS. Slit-lamp evaluation revealed 1+ bulbar conjunctival injection OU, intact corneal epithelium OU, and no cells or flare in the anterior chambers OU. Due to improving punctate epitheliopathy, the frequency of the antibiotic drops, the prednisolone, and the artificial tears was reduced to bid. After 3 days, he was instructed to discontinue them. The patient was scheduled to return in 2 weeks for an anterior segment follow-up.

At the next follow-up visit, the patient reported that his vision had returned to normal, and he had no further ocular AEs. His best-corrected visual acuity was 20/20-2 OD and 20/20 OS. Slit-lamp evaluation revealed mild blepharitis OU, trace bulbar conjunctival injection OU, and complete resolution of the keratitis OU. The assessment was acute allergic conjunctivitis thought to be secondary to an AE to proparacaine OU, yet the need to rule out hypersensitivity to tropicamide and/or phenylephrine remained. The plan was to educate the patient of the possibility of allergic reaction on future visits and to recommend continued use of artificial tears as needed.

Through a careful and extensive chart review of all past visits, it was suspected that phenylephrine might be to blame rather than proparacaine. At the subsequent visit, the patient agreed to undergo testing to determine the culprit via instillation of proparacaine in one eye and tropicamide in the other. The patient had no reaction to either drop (checked 45 minutes after instillation and the following day). By process of elimination, phenylephrine was determined to be the offending agent.

Discussion

Following a thorough review of the patient’s chart, it was found that on other occasions he had presented with suspected allergic reactions following routine eye examinations. The patient reported he had experienced a reaction in 2007 but could not recall what drops were instilled in his eyes at the time. In addition, there was no documentation in his medical record of the subsequent reaction following that visit. Another reaction occurred in July 2010 with instillation of tropicamide 1%, phenylephrine 2.5%, and Fluress (fluorescein sodium and benoxinate hydrochloride ophthalmic solution USP). In October 2013, when tropicamide 0.5%, proparacaine, and fluorescein strips were instilled, there was no reaction. The next reaction occurred in October 2014, when tropicamide 0.5%, phenylephrine 2.5%, proparacaine, and fluorescein strips were instilled.

This careful review of past exam notes revealed that phenylephrine and Fluress were the only drops that had not been instilled at the October 2013 visit when no AE was reported. However, Fluress was an unlikely culprit since it was not instilled in October 2014, and the patient still experienced an AE. Therefore, the agent most likely responsible for the allergic reaction in the patient, as confirmed by a review of the past notes and by the aforementioned pharmacologic test, was deemed to be phenylephrine (Table).

Adverse reactions to topical ocular medications and specifically to diagnostic eye drops have long been recognized. Mathias, Camarasa, Barber, Ducombs, and Monsálvezhave reported on variations of conjunctivitis and periorbital erythema with positive patch testing to phenylephrine.^1-5 Geyer and colleagues reported on a study of 21 patients who had blepharoconjunctivitis after instillation of phenylephrine.⁶ In this case study patient, severe keratoconjunctivitis was the clinical manifestation observed.

Villarreal and colleagues studied 31 patients who had a previous reaction to mydriatic drops. The study found that phenylephrine was the drug that most frequently caused an AE (93.5%).⁷ One patient reacted to the preservative thimerosal, and 1 patient reacted to benoxiprocaine. Tropicamide was demonstrated to be very well tolerated as none of the patients tested positive on either the patch test or the pharmacologic test.

Tropicamide is a nonselective muscarinic antagonist commonly used for mydriasis due to its fast onset and short duration.⁸ Adverse reactions to tropicamide are rare. Three studies reported on patients who had a positive patch test to tropicamide.^9-11 However, the reaction was not provoked by direct instillation of tropicamide into the eye.

Common in-office topical anesthetics, proparacaine, tetracaine, benoxinate, and lidocaine also can cause AEs. Corneal toxicity is a well-known complication with topical anesthetic abuse, whereas allergic reactions are considered rare. The most common symptoms include stingingand discomfort upon instillation. Common signs include punctate corneal epithelial erosionsresulting indirectly from a decrease in reflex tearing, infrequent blinking, and increased tear evaporation.¹² Topical anesthetics also inhibit the migration of corneal epithelial cells and cause direct damage to the cells that are present, leading to impaired healing and epithelial defects.¹³

Manifestations of allergic reaction to topical anesthetics can include conjunctival hyperemia and edema, edematous eyelids, and lacrimation. One published case described a 60-year-old woman who developed eczematous dermatitis of the eyelids after ophthalmic anesthetic drops were instilled prior to laser surgery. Patch testing showed a positive response to benzocaine 5%, proparacaine, and tetracaine 0.5%.¹⁴

Preservatives, in general, can cause an allergic reaction. Benzalkonium chloride’s (BAK) cytotoxic sequelae include possible trabecular cell death in glaucoma patients, disruption of tear film stability (even at low concentrations), and immune-allergenic properties. One article reported BAK as one of the 30 most frequent allergens causing allergic periorbital dermatitis.¹⁵ Benzalkonium chloride is used in most brands of phenylephrine. However, preservatives in this patient’s case were ruled out as instigating agents since both phenylephrine and tropicamide contain the same preservative, BAK 0.01%, yet this patient did not develop a reaction to tropicamide when used without phenylephrine. Expired medications also were not considered to be a factor as none of the medications used on the patient were indeed expired (the Malcom Randall VAMC clinic maintains a strict policy of discarding medications 28 days after being opened).

Although uncommon, phenylephrine sometimes has been found to cause a type 4 hypersensitivity reaction, also known as cell-mediated or delayed-type hypersensitivity.¹⁶ First, helper T cells secrete cytokines. Activation of cytokines recruits and activates cytotoxic T cells, monocytes, and macrophages, leading to inflammation of the surrounding tissue. Examples of cell-mediated hypersensitivity include reactions to the tuberculin skin test and to poison ivy.

Type 1 hypersensitivity reactions, also known as immediate or anaphylactic hypersensitivity reactions, are not triggered by phenylephrine. In this type of reaction, IgE binds to the mast cell on initial exposure to an allergen. On second exposure, the allergen binds to the IgE, causing the mast cell to release mediators of inflammation, triggering physiologic responses. Examples of this type of hypersensitivity include those seen with penicillin, bee stings, hay fever, bronchial asthma, and food allergies, for example, to shellfish.

A toxic reaction’s mechanism differs from that of a type 4 hypersensitivity reaction. Toxic reactions occur due to direct cytotoxicity of a drug caused by a low or high pH and either hyper- or hypo-osmolarity. Toxicity can lead to corneal and conjunctival cell necrosis or induce apoptosis, stimulating inflammatory reactions. Clinically, toxic reactions will present with follicles, whereas allergic reactions will present with papillae.

The definitive diagnostic methods used to determine the allergic agent causing ocular or periocular AEs are patch testing and conjunctival challenge.⁷ Mathias, Camarasa, Barber, Ducombs,and Monsálvezused patch testing to confirm phenylephrine as the allergic agent in their series of cases. Patch testing entails the application of a small amount of an allergic agent that is taped onto the skin. The allergic agent is confirmed if the patient has a dermal reaction, wherein the area patched will become erythematous. When patch testing is negative or inconclusive, a conjunctival challenge is performed by instillation of the suspected allergic agent into the eye with subsequent observation to determine whether a reaction occurs. The sequelae found in Villarreal’s study included itching, lacrimation, edema, erythema, and sometimes blepharitis.⁷

A direct conjunctival challenge with the suspected culprit was not pursued in this patient’s case due to the known severity of the potential resulting reaction. The authors instead chose an indirect method of determining the implicating agent and used the process of elimination to whittle down the most likely suspect. A challenge with the medications suspected not to be likely offenders was undertaken. This spared the patient a likely repeat of the AE he had just recovered from.

Management

Allergic reactions can resolve without medical intervention. The first step is to remove the allergen. For delayed hypersensitivity reactions, treatments may include topical decongestants, cool compresses, and corticosteroids.⁸ The treatment for immediate hypersensitivity reaction differs from that of delayed hypersensitivity reaction in that antihistamines are used.^17,18

This patient reported receiving no treatment for his ocular symptoms following eye examinations in the past, yet he experienced complete resolution after each AE. In this case, both a steroid and a prophylactic antibiotic to facilitate a more rapid improvement were used.

Conclusion

Although uncommon, cases of allergic reaction to phenylephrine can occur. The incidence of phenylephrine allergy is 0.6%.6 The case study patient presented with a severe keratoconjunctivitis following routine eye examination with an accompanying history of adverse ocular signs and symptoms following multiple past exams.

It is important for all eye care clinicians to realize that AEs to diagnostic eye drops are possible and can occur following the most routine of visits. Such reactions can be caused by dilating agents, anesthetics, or preservatives, and these may be allergic or toxic. Clinicians should take special care to identify the instigating agent, and if possible, to avoid using such agents on patients during future exams. Clinicians also should understand how best to manage iatrogenic AEs when they encounter them in order to restore a patient’s visual function as quickly as possible.

Phenylephrine, a sympathomimetic drug, is commonly used in eye exams to dilate the pupil of the eye and to differentiate scleritis from episcleritis. Common adverse effects (AEs) of phenylephrine include subjective burning, stinging with lacrimation, rebound hyperemia, and liberation of iris pigment into the anterior chamber. Less common, systemic AEs include tachycardia and elevation of systemic blood pressure. Although instances of allergic reactions are rare, phenylephrine has been reported to cause contact dermatitis, blepharoconjunctivitis, and as in this case, keratoconjunctivitis.

Case Report

An 83-year-old white male presented for a red eye evaluation 2 days after having undergone a comprehensive eye exam with dilation at the Malcom Randall VAMC clinic in Gainesville, Florida. The patient reported onset of blurred vision, which he described as looking through a fog. He further compared the feeling to pins sticking in his eyes. The patient noted he had experienced similar symptoms on a few other occasions following eye exams. At the most recent eye exam, proparacaine and fluorescein had been used for tonometry, and phenylephrine 2.5% and tropicamide 0.5% had been used for pupillary dilation.

The patient’s best-corrected visual acuity was counting fingers at 2 feet in the right eye (OD) and left eye (OS). The best-corrected visual acuity 2 days prior had been 20/20 OD and OS. Pupils and extraocular motilities were unremarkable. Intraocular pressures were not obtained due to concern for a possible adverse reaction to proparacaine.

Slit-lamp evaluation revealed the lids to be lax, erythematous, and edematous in both eyes (Figure 1).

The initial diagnosis was acute chemical conjunctivitis most likely due to an AE to proparacaine. The plan was to start the patient on antibiotic eye drops qid OU, prednisolone qid OU, and artificial tears every hour OU. The patient was scheduled to return to clinic 4 days later for an anterior segment follow-up.

At the follow-up visit, the patient reported significant visual improvement. His best-corrected visual acuity was 20/40-2 without improvement on pinhole OD and 20/50-2 with improvement to 20/30+ on pinhole OS. Slit-lamp evaluation revealed 1+ bulbar conjunctival injection OU, intact corneal epithelium OU, and no cells or flare in the anterior chambers OU. Due to improving punctate epitheliopathy, the frequency of the antibiotic drops, the prednisolone, and the artificial tears was reduced to bid. After 3 days, he was instructed to discontinue them. The patient was scheduled to return in 2 weeks for an anterior segment follow-up.

At the next follow-up visit, the patient reported that his vision had returned to normal, and he had no further ocular AEs. His best-corrected visual acuity was 20/20-2 OD and 20/20 OS. Slit-lamp evaluation revealed mild blepharitis OU, trace bulbar conjunctival injection OU, and complete resolution of the keratitis OU. The assessment was acute allergic conjunctivitis thought to be secondary to an AE to proparacaine OU, yet the need to rule out hypersensitivity to tropicamide and/or phenylephrine remained. The plan was to educate the patient of the possibility of allergic reaction on future visits and to recommend continued use of artificial tears as needed.

Through a careful and extensive chart review of all past visits, it was suspected that phenylephrine might be to blame rather than proparacaine. At the subsequent visit, the patient agreed to undergo testing to determine the culprit via instillation of proparacaine in one eye and tropicamide in the other. The patient had no reaction to either drop (checked 45 minutes after instillation and the following day). By process of elimination, phenylephrine was determined to be the offending agent.

Discussion

Following a thorough review of the patient’s chart, it was found that on other occasions he had presented with suspected allergic reactions following routine eye examinations. The patient reported he had experienced a reaction in 2007 but could not recall what drops were instilled in his eyes at the time. In addition, there was no documentation in his medical record of the subsequent reaction following that visit. Another reaction occurred in July 2010 with instillation of tropicamide 1%, phenylephrine 2.5%, and Fluress (fluorescein sodium and benoxinate hydrochloride ophthalmic solution USP). In October 2013, when tropicamide 0.5%, proparacaine, and fluorescein strips were instilled, there was no reaction. The next reaction occurred in October 2014, when tropicamide 0.5%, phenylephrine 2.5%, proparacaine, and fluorescein strips were instilled.

This careful review of past exam notes revealed that phenylephrine and Fluress were the only drops that had not been instilled at the October 2013 visit when no AE was reported. However, Fluress was an unlikely culprit since it was not instilled in October 2014, and the patient still experienced an AE. Therefore, the agent most likely responsible for the allergic reaction in the patient, as confirmed by a review of the past notes and by the aforementioned pharmacologic test, was deemed to be phenylephrine (Table).

Adverse reactions to topical ocular medications and specifically to diagnostic eye drops have long been recognized. Mathias, Camarasa, Barber, Ducombs, and Monsálvezhave reported on variations of conjunctivitis and periorbital erythema with positive patch testing to phenylephrine.^1-5 Geyer and colleagues reported on a study of 21 patients who had blepharoconjunctivitis after instillation of phenylephrine.⁶ In this case study patient, severe keratoconjunctivitis was the clinical manifestation observed.

Villarreal and colleagues studied 31 patients who had a previous reaction to mydriatic drops. The study found that phenylephrine was the drug that most frequently caused an AE (93.5%).⁷ One patient reacted to the preservative thimerosal, and 1 patient reacted to benoxiprocaine. Tropicamide was demonstrated to be very well tolerated as none of the patients tested positive on either the patch test or the pharmacologic test.

Tropicamide is a nonselective muscarinic antagonist commonly used for mydriasis due to its fast onset and short duration.⁸ Adverse reactions to tropicamide are rare. Three studies reported on patients who had a positive patch test to tropicamide.^9-11 However, the reaction was not provoked by direct instillation of tropicamide into the eye.

Common in-office topical anesthetics, proparacaine, tetracaine, benoxinate, and lidocaine also can cause AEs. Corneal toxicity is a well-known complication with topical anesthetic abuse, whereas allergic reactions are considered rare. The most common symptoms include stingingand discomfort upon instillation. Common signs include punctate corneal epithelial erosionsresulting indirectly from a decrease in reflex tearing, infrequent blinking, and increased tear evaporation.¹² Topical anesthetics also inhibit the migration of corneal epithelial cells and cause direct damage to the cells that are present, leading to impaired healing and epithelial defects.¹³

Manifestations of allergic reaction to topical anesthetics can include conjunctival hyperemia and edema, edematous eyelids, and lacrimation. One published case described a 60-year-old woman who developed eczematous dermatitis of the eyelids after ophthalmic anesthetic drops were instilled prior to laser surgery. Patch testing showed a positive response to benzocaine 5%, proparacaine, and tetracaine 0.5%.¹⁴

Preservatives, in general, can cause an allergic reaction. Benzalkonium chloride’s (BAK) cytotoxic sequelae include possible trabecular cell death in glaucoma patients, disruption of tear film stability (even at low concentrations), and immune-allergenic properties. One article reported BAK as one of the 30 most frequent allergens causing allergic periorbital dermatitis.¹⁵ Benzalkonium chloride is used in most brands of phenylephrine. However, preservatives in this patient’s case were ruled out as instigating agents since both phenylephrine and tropicamide contain the same preservative, BAK 0.01%, yet this patient did not develop a reaction to tropicamide when used without phenylephrine. Expired medications also were not considered to be a factor as none of the medications used on the patient were indeed expired (the Malcom Randall VAMC clinic maintains a strict policy of discarding medications 28 days after being opened).

Although uncommon, phenylephrine sometimes has been found to cause a type 4 hypersensitivity reaction, also known as cell-mediated or delayed-type hypersensitivity.¹⁶ First, helper T cells secrete cytokines. Activation of cytokines recruits and activates cytotoxic T cells, monocytes, and macrophages, leading to inflammation of the surrounding tissue. Examples of cell-mediated hypersensitivity include reactions to the tuberculin skin test and to poison ivy.

Type 1 hypersensitivity reactions, also known as immediate or anaphylactic hypersensitivity reactions, are not triggered by phenylephrine. In this type of reaction, IgE binds to the mast cell on initial exposure to an allergen. On second exposure, the allergen binds to the IgE, causing the mast cell to release mediators of inflammation, triggering physiologic responses. Examples of this type of hypersensitivity include those seen with penicillin, bee stings, hay fever, bronchial asthma, and food allergies, for example, to shellfish.

A toxic reaction’s mechanism differs from that of a type 4 hypersensitivity reaction. Toxic reactions occur due to direct cytotoxicity of a drug caused by a low or high pH and either hyper- or hypo-osmolarity. Toxicity can lead to corneal and conjunctival cell necrosis or induce apoptosis, stimulating inflammatory reactions. Clinically, toxic reactions will present with follicles, whereas allergic reactions will present with papillae.

The definitive diagnostic methods used to determine the allergic agent causing ocular or periocular AEs are patch testing and conjunctival challenge.⁷ Mathias, Camarasa, Barber, Ducombs,and Monsálvezused patch testing to confirm phenylephrine as the allergic agent in their series of cases. Patch testing entails the application of a small amount of an allergic agent that is taped onto the skin. The allergic agent is confirmed if the patient has a dermal reaction, wherein the area patched will become erythematous. When patch testing is negative or inconclusive, a conjunctival challenge is performed by instillation of the suspected allergic agent into the eye with subsequent observation to determine whether a reaction occurs. The sequelae found in Villarreal’s study included itching, lacrimation, edema, erythema, and sometimes blepharitis.⁷

A direct conjunctival challenge with the suspected culprit was not pursued in this patient’s case due to the known severity of the potential resulting reaction. The authors instead chose an indirect method of determining the implicating agent and used the process of elimination to whittle down the most likely suspect. A challenge with the medications suspected not to be likely offenders was undertaken. This spared the patient a likely repeat of the AE he had just recovered from.

Management

Allergic reactions can resolve without medical intervention. The first step is to remove the allergen. For delayed hypersensitivity reactions, treatments may include topical decongestants, cool compresses, and corticosteroids.⁸ The treatment for immediate hypersensitivity reaction differs from that of delayed hypersensitivity reaction in that antihistamines are used.^17,18

This patient reported receiving no treatment for his ocular symptoms following eye examinations in the past, yet he experienced complete resolution after each AE. In this case, both a steroid and a prophylactic antibiotic to facilitate a more rapid improvement were used.

Conclusion

Although uncommon, cases of allergic reaction to phenylephrine can occur. The incidence of phenylephrine allergy is 0.6%.6 The case study patient presented with a severe keratoconjunctivitis following routine eye examination with an accompanying history of adverse ocular signs and symptoms following multiple past exams.

It is important for all eye care clinicians to realize that AEs to diagnostic eye drops are possible and can occur following the most routine of visits. Such reactions can be caused by dilating agents, anesthetics, or preservatives, and these may be allergic or toxic. Clinicians should take special care to identify the instigating agent, and if possible, to avoid using such agents on patients during future exams. Clinicians also should understand how best to manage iatrogenic AEs when they encounter them in order to restore a patient’s visual function as quickly as possible.

Phenylephrine, a sympathomimetic drug, is commonly used in eye exams to dilate the pupil of the eye and to differentiate scleritis from episcleritis. Common adverse effects (AEs) of phenylephrine include subjective burning, stinging with lacrimation, rebound hyperemia, and liberation of iris pigment into the anterior chamber. Less common, systemic AEs include tachycardia and elevation of systemic blood pressure. Although instances of allergic reactions are rare, phenylephrine has been reported to cause contact dermatitis, blepharoconjunctivitis, and as in this case, keratoconjunctivitis.

Case Report

An 83-year-old white male presented for a red eye evaluation 2 days after having undergone a comprehensive eye exam with dilation at the Malcom Randall VAMC clinic in Gainesville, Florida. The patient reported onset of blurred vision, which he described as looking through a fog. He further compared the feeling to pins sticking in his eyes. The patient noted he had experienced similar symptoms on a few other occasions following eye exams. At the most recent eye exam, proparacaine and fluorescein had been used for tonometry, and phenylephrine 2.5% and tropicamide 0.5% had been used for pupillary dilation.

The patient’s best-corrected visual acuity was counting fingers at 2 feet in the right eye (OD) and left eye (OS). The best-corrected visual acuity 2 days prior had been 20/20 OD and OS. Pupils and extraocular motilities were unremarkable. Intraocular pressures were not obtained due to concern for a possible adverse reaction to proparacaine.

Slit-lamp evaluation revealed the lids to be lax, erythematous, and edematous in both eyes (Figure 1).

The initial diagnosis was acute chemical conjunctivitis most likely due to an AE to proparacaine. The plan was to start the patient on antibiotic eye drops qid OU, prednisolone qid OU, and artificial tears every hour OU. The patient was scheduled to return to clinic 4 days later for an anterior segment follow-up.

At the follow-up visit, the patient reported significant visual improvement. His best-corrected visual acuity was 20/40-2 without improvement on pinhole OD and 20/50-2 with improvement to 20/30+ on pinhole OS. Slit-lamp evaluation revealed 1+ bulbar conjunctival injection OU, intact corneal epithelium OU, and no cells or flare in the anterior chambers OU. Due to improving punctate epitheliopathy, the frequency of the antibiotic drops, the prednisolone, and the artificial tears was reduced to bid. After 3 days, he was instructed to discontinue them. The patient was scheduled to return in 2 weeks for an anterior segment follow-up.

At the next follow-up visit, the patient reported that his vision had returned to normal, and he had no further ocular AEs. His best-corrected visual acuity was 20/20-2 OD and 20/20 OS. Slit-lamp evaluation revealed mild blepharitis OU, trace bulbar conjunctival injection OU, and complete resolution of the keratitis OU. The assessment was acute allergic conjunctivitis thought to be secondary to an AE to proparacaine OU, yet the need to rule out hypersensitivity to tropicamide and/or phenylephrine remained. The plan was to educate the patient of the possibility of allergic reaction on future visits and to recommend continued use of artificial tears as needed.

Through a careful and extensive chart review of all past visits, it was suspected that phenylephrine might be to blame rather than proparacaine. At the subsequent visit, the patient agreed to undergo testing to determine the culprit via instillation of proparacaine in one eye and tropicamide in the other. The patient had no reaction to either drop (checked 45 minutes after instillation and the following day). By process of elimination, phenylephrine was determined to be the offending agent.

Discussion

Following a thorough review of the patient’s chart, it was found that on other occasions he had presented with suspected allergic reactions following routine eye examinations. The patient reported he had experienced a reaction in 2007 but could not recall what drops were instilled in his eyes at the time. In addition, there was no documentation in his medical record of the subsequent reaction following that visit. Another reaction occurred in July 2010 with instillation of tropicamide 1%, phenylephrine 2.5%, and Fluress (fluorescein sodium and benoxinate hydrochloride ophthalmic solution USP). In October 2013, when tropicamide 0.5%, proparacaine, and fluorescein strips were instilled, there was no reaction. The next reaction occurred in October 2014, when tropicamide 0.5%, phenylephrine 2.5%, proparacaine, and fluorescein strips were instilled.

This careful review of past exam notes revealed that phenylephrine and Fluress were the only drops that had not been instilled at the October 2013 visit when no AE was reported. However, Fluress was an unlikely culprit since it was not instilled in October 2014, and the patient still experienced an AE. Therefore, the agent most likely responsible for the allergic reaction in the patient, as confirmed by a review of the past notes and by the aforementioned pharmacologic test, was deemed to be phenylephrine (Table).

Adverse reactions to topical ocular medications and specifically to diagnostic eye drops have long been recognized. Mathias, Camarasa, Barber, Ducombs, and Monsálvezhave reported on variations of conjunctivitis and periorbital erythema with positive patch testing to phenylephrine.^1-5 Geyer and colleagues reported on a study of 21 patients who had blepharoconjunctivitis after instillation of phenylephrine.⁶ In this case study patient, severe keratoconjunctivitis was the clinical manifestation observed.

Villarreal and colleagues studied 31 patients who had a previous reaction to mydriatic drops. The study found that phenylephrine was the drug that most frequently caused an AE (93.5%).⁷ One patient reacted to the preservative thimerosal, and 1 patient reacted to benoxiprocaine. Tropicamide was demonstrated to be very well tolerated as none of the patients tested positive on either the patch test or the pharmacologic test.

Tropicamide is a nonselective muscarinic antagonist commonly used for mydriasis due to its fast onset and short duration.⁸ Adverse reactions to tropicamide are rare. Three studies reported on patients who had a positive patch test to tropicamide.^9-11 However, the reaction was not provoked by direct instillation of tropicamide into the eye.

Common in-office topical anesthetics, proparacaine, tetracaine, benoxinate, and lidocaine also can cause AEs. Corneal toxicity is a well-known complication with topical anesthetic abuse, whereas allergic reactions are considered rare. The most common symptoms include stingingand discomfort upon instillation. Common signs include punctate corneal epithelial erosionsresulting indirectly from a decrease in reflex tearing, infrequent blinking, and increased tear evaporation.¹² Topical anesthetics also inhibit the migration of corneal epithelial cells and cause direct damage to the cells that are present, leading to impaired healing and epithelial defects.¹³

Manifestations of allergic reaction to topical anesthetics can include conjunctival hyperemia and edema, edematous eyelids, and lacrimation. One published case described a 60-year-old woman who developed eczematous dermatitis of the eyelids after ophthalmic anesthetic drops were instilled prior to laser surgery. Patch testing showed a positive response to benzocaine 5%, proparacaine, and tetracaine 0.5%.¹⁴

Preservatives, in general, can cause an allergic reaction. Benzalkonium chloride’s (BAK) cytotoxic sequelae include possible trabecular cell death in glaucoma patients, disruption of tear film stability (even at low concentrations), and immune-allergenic properties. One article reported BAK as one of the 30 most frequent allergens causing allergic periorbital dermatitis.¹⁵ Benzalkonium chloride is used in most brands of phenylephrine. However, preservatives in this patient’s case were ruled out as instigating agents since both phenylephrine and tropicamide contain the same preservative, BAK 0.01%, yet this patient did not develop a reaction to tropicamide when used without phenylephrine. Expired medications also were not considered to be a factor as none of the medications used on the patient were indeed expired (the Malcom Randall VAMC clinic maintains a strict policy of discarding medications 28 days after being opened).

Although uncommon, phenylephrine sometimes has been found to cause a type 4 hypersensitivity reaction, also known as cell-mediated or delayed-type hypersensitivity.¹⁶ First, helper T cells secrete cytokines. Activation of cytokines recruits and activates cytotoxic T cells, monocytes, and macrophages, leading to inflammation of the surrounding tissue. Examples of cell-mediated hypersensitivity include reactions to the tuberculin skin test and to poison ivy.

Type 1 hypersensitivity reactions, also known as immediate or anaphylactic hypersensitivity reactions, are not triggered by phenylephrine. In this type of reaction, IgE binds to the mast cell on initial exposure to an allergen. On second exposure, the allergen binds to the IgE, causing the mast cell to release mediators of inflammation, triggering physiologic responses. Examples of this type of hypersensitivity include those seen with penicillin, bee stings, hay fever, bronchial asthma, and food allergies, for example, to shellfish.

A toxic reaction’s mechanism differs from that of a type 4 hypersensitivity reaction. Toxic reactions occur due to direct cytotoxicity of a drug caused by a low or high pH and either hyper- or hypo-osmolarity. Toxicity can lead to corneal and conjunctival cell necrosis or induce apoptosis, stimulating inflammatory reactions. Clinically, toxic reactions will present with follicles, whereas allergic reactions will present with papillae.

The definitive diagnostic methods used to determine the allergic agent causing ocular or periocular AEs are patch testing and conjunctival challenge.⁷ Mathias, Camarasa, Barber, Ducombs,and Monsálvezused patch testing to confirm phenylephrine as the allergic agent in their series of cases. Patch testing entails the application of a small amount of an allergic agent that is taped onto the skin. The allergic agent is confirmed if the patient has a dermal reaction, wherein the area patched will become erythematous. When patch testing is negative or inconclusive, a conjunctival challenge is performed by instillation of the suspected allergic agent into the eye with subsequent observation to determine whether a reaction occurs. The sequelae found in Villarreal’s study included itching, lacrimation, edema, erythema, and sometimes blepharitis.⁷

A direct conjunctival challenge with the suspected culprit was not pursued in this patient’s case due to the known severity of the potential resulting reaction. The authors instead chose an indirect method of determining the implicating agent and used the process of elimination to whittle down the most likely suspect. A challenge with the medications suspected not to be likely offenders was undertaken. This spared the patient a likely repeat of the AE he had just recovered from.

Management

Allergic reactions can resolve without medical intervention. The first step is to remove the allergen. For delayed hypersensitivity reactions, treatments may include topical decongestants, cool compresses, and corticosteroids.⁸ The treatment for immediate hypersensitivity reaction differs from that of delayed hypersensitivity reaction in that antihistamines are used.^17,18

This patient reported receiving no treatment for his ocular symptoms following eye examinations in the past, yet he experienced complete resolution after each AE. In this case, both a steroid and a prophylactic antibiotic to facilitate a more rapid improvement were used.

Conclusion

Although uncommon, cases of allergic reaction to phenylephrine can occur. The incidence of phenylephrine allergy is 0.6%.6 The case study patient presented with a severe keratoconjunctivitis following routine eye examination with an accompanying history of adverse ocular signs and symptoms following multiple past exams.

It is important for all eye care clinicians to realize that AEs to diagnostic eye drops are possible and can occur following the most routine of visits. Such reactions can be caused by dilating agents, anesthetics, or preservatives, and these may be allergic or toxic. Clinicians should take special care to identify the instigating agent, and if possible, to avoid using such agents on patients during future exams. Clinicians also should understand how best to manage iatrogenic AEs when they encounter them in order to restore a patient’s visual function as quickly as possible.