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History A 51 year-old female with a history of chronic dry eyes and photosensitivity was referred for evaluation. She reported a five year history of symptoms of frequent irritation and photophobia in both eyes that were mildly improved with artificial tears, punctal plugs and Restasis. In addition, she had experienced recurrent episodes of pain and irritation in the left eye since suffering a corneal abrasion in the same eye a few months prior. These symptoms were especially worse in the morning upon waking up. She had no significant past medical history. Examination On examination, CDVA was 20/20 in the right eye and 20/40 in the left eye. Slit lamp examination revealed central punctate epithelial keratopathy and scattered negative fluorescein staining in both eyes but more prominent in the left eye. Subtle epithelial map lines were present without subepithelial scarring in both eyes. The anterior chambers were deep and quiet and trace nuclear sclerotic changes were noted in both eyes. The posterior segment examination was unremarkable. Diagnosis/Course The patient was diagnosed with recurrent corneal erosions secondary to epithelial basement membrane dystrophy (EBMD). She was started on hypertonic sodium chloride drops with minimal improvement of her symptoms. After a discussion of additional treatment options, the patient opted for epithelial debridement instead of extended wear of bandage contact lenses. She underwent epithelial debridement and diamond burr polishing of Bowman layer uneventfully in her left eye. Gatifloxacin and prednisolone acetate drops were initiated postoperatively. Her postoperative course was notable for slow corneal re-epithelialization initially attributed to dry eyes and a suboptimal ocular surface. However, at the postoperative day 10 visit, the edges of the persistent epithelial defect in her left eye appeared irregular and dendritic without underlying stromal involvement. The dendritic branches stained with fluorescein. A diagnosis of HSV epithelial keratitis was made. Treatment The patient was started on oral acyclovir and the frequency of the topical corticosteroid was decreased. Four days after starting acyclovir the epithelial defect resolved with mild subepithelial scarring. One week after initiating treatment the patient s vision in the left eye returned to 20/20 with minimal subepithelial haze. Discussion EBMD often presents with subtle clinical features and many affected individuals may remain asymptomatic throughout their lives. Presenting symptoms may include decreased visual acuity, dry eye symptoms, or recurrent corneal erosions. Initially, clinical signs associated with EBMD may be subtle, although a history of recurrent erosions should

suggest this diagnosis. With repeated cycles of epithelial breakdown and cell turnover, morphologic changes occur in the epithelial basement membrane, which manifests as corneal epithelial map lines, fingerprint lines and/or microcysts. Treatment of recurrent corneal erosion ranges from conservative measures, such as lubrication, application of a hyperosmotic agent and bandage soft contact lens wear, to surgical approaches, such as anterior stromal micropuncture, phototherapeutic keratectomy (PTK), or epithelial debridement with or without diamond burr polishing. 1 Delayed epithelial healing in our patient after an uneventful epithelial debridement and diamond burr polishing was attributed initially to dry eyes with a suboptimal ocular surface. However it later became evident that a secondary HSV epithelial keratitis was involved. It was unclear in this case if HSV keratitis was the cause of the persistent epithelial defect or resulted from it. Several factors including psychological stress, systemic infection, sunlight exposure, menstruation and trauma have been suggested as potential triggers of recurrent ocular HSV disease but were not confirmed by the Herpetic Eye Disease Study (HEDS) and remain controversial. 2 The occurrence of HSV keratitis have been reported in cases of ocular surface disturbance, for example, after cataract surgery 3, PTK 4, LASIK 5, and cross-linking 6. The use of topical corticosteroids and mechanical trauma caused by epithelial debridement may be potential risk factors in this case. Conclusion EBMD and recurrent corneal erosions should be on the differential diagnosis for patients presenting with dry eye symptoms unrelieved by medical therapy. A careful history is vital early in the course of the disease when clinical signs may be subtle or absent. HSV epithelial keratitis may be associated with delayed epithelial healing after epithelial debridement and clinical vigilance is essential in its recognition. Acknowledgements Anthony Aldave, MD

References 1. Vo RC, Chen JL, Sanchez PJ, Yu F, Aldave AJ. Long- term outcomes of epithelial debridement and diamond burr polishing for corneal epithelial irregularity and recurrent corneal erosion. Cornea. Oct 2015;34(10):1259-1265. 2. Psychological stress and other potential triggers for recurrences of herpes simplex virus eye infections. Herpetic Eye Disease Study Group. Arch Ophthalmol. Dec 2000;118(12):1617-1625. 3. Barequet IS, Wasserzug Y. Herpes simplex keratitis after cataract surgery. Cornea. Jun 2007;26(5):615-617. 4. Lu CK, Chen KH, Lee SM, Hsu WM, Lai JY, Li YS. Herpes simplex keratitis following excimer laser application. J Refract Surg. May 2006;22(5):509-511. 5. Arora T, Sharma N, Arora S, Titiyal JS. Fulminant herpetic keratouveitis with flap necrosis following laser in situ keratomileusis: Case report and review of literature. J Cataract Refract Surg. Dec 2014;40(12):2152-2156. 6. Kymionis GD, Portaliou DM, Bouzoukis DI, et al. Herpetic keratitis with iritis after corneal crosslinking with riboflavin and ultraviolet A for keratoconus. J Cataract Refract Surg. Nov 2007;33(11):1982-1984.

Rough around the edges Daniel Su, MD

Presentation HPI: 51 year-old female with chronic dry eyes and photosensitivity referred for evaluation. Frequent irritation, photophobia x 5 years Mild improvement with artificial tears, punctal plugs, and Restasis Recent corneal abrasion OS, with recurrent pain OS, especially worse in the morning

Presentation POH: Dry eyes Allergies: NKDA Ocular Rx: AFTs FHx: noncontributory PMH: None SHx: noncontributory Meds: Occasional Tylenol

Examination Vasc OD 20/20 OS 20/40 No APD EOM/CVF full OU IOP 16 OU

Examination Lids/Lashes Right Trace blepharitis, no plugs in place Left Trace blepharitis, no plugs in place Conjunctiva/Sclera Trace injection Trace injection Cornea Central PEK with scattered negative staining. Epithelial map lines at 1 o clock. No ED, central PEK, negative staining, scattered epithelial map lines, most prominent at 8 o clock, no subepi scarring Anterior Chamber Deep and Quiet Deep and Quiet Iris Normal Normal Lens Tr NS Tr NS

Examination Dilated fundus exam normal

Slit Lamp Photos

Course Recurrent corneal erosions secondary to EBMD Started on hypertonic NaCl drops with minimal improvement Discussed extended BCTL wear vs epithelial debridement with diamond burr polishing

POD 7

POD 7

Delayed epithelial healing - DDx Dry eyes Mechanical (abn. lid pathology) Inflammatory Neurotrophic Secondary Infection Bacterial Viral Systemic Diabetes Malnutrition Limbal stem cell deficiency Toxic epitheliopathy

POD 10

POD 10

Course Morphologic change in the edge of the epithelial defect Highly suspicious for HSV epithelial keratitis Started on oral acyclovir Tapered off topical steroids

Four days later

Four days later

Secondary HSV Keratitis Psychological stress, systemic infection, sunlight exposure, menstruation, and trauma have been implicated as potential triggers The Herpetic Eye Disease Study (HEDS) did not confirm these factors Have also been reported after cataract surgery, PTK, LASIK, and cross-linking for keratoconus

Secondary HSV Keratitis Unclear if HSV attributed to delayed epithelialization in the current case or was result of it Topical corticosteroids and mechanical trauma from epithelial debridement may be potential risk factors involved

Summary Recurrent corneal erosions and EBMD should be on the differential diagnosis for patients presenting with dry eyes unimproved/or recurrent despite medical therapy HSV keratitis may be associated with delayed epithelial healing after mechanical debridement. Clinical vigilance is essential in its recognition

References 1. Vo RC, Chen JL, Sanchez PJ, Yu F, Aldave AJ. Long-Term Outcomes of Epithelial Debridement and Diamond Burr Polishing for Corneal Epithelial Irregularity and Recurrent Corneal Erosion. Cornea. Oct 2015;;34(10):1259-1265. 2. Psychological stress and other potential triggers for recurrences of herpes simplex virus eye infections. Herpetic Eye Disease Study Group. Arch Ophthalmol. Dec 2000;;118(12):1617-1625. 3.Barequet IS, Wasserzug Y. Herpes simplex keratitis after cataract surgery. Cornea. Jun 2007;;26(5):615-617. 4. Lu CK, Chen KH, Lee SM, Hsu WM, Lai JY, Li YS. Herpes simplex keratitis following excimer laser application. J Refract Surg. May 2006;;22(5):509-511. 5. Arora T, Sharma N, Arora S, Titiyal JS. Fulminant herpetic keratouveitis with flap necrosis following laser in situ keratomileusis: Case report and review of literature. J Cataract Refract Surg. Dec 2014;;40(12):2152-2156. 6. Kymionis GD, Portaliou DM, Bouzoukis DI, et al. Herpetic keratitis with iritis after corneal crosslinking with riboflavin and ultraviolet A for keratoconus. J Cataract Refract Surg. Nov 2007;;33(11):1982-1984.