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Introduction: The term Corneal Dystrophy refers to a rare heterogeneous group of genetically determined, bilateral, symmetric, primary diseases, restricted to cornea and not associated with previous ocular inflammation. The dystrophies are classified based on the layer of cornea involved, into superficial, stromal and posterior dystrophies, each of which is genetically determined. Though the clinical features are often characteristic, definitive diagnosis is possible only after histological examination. The management protocols and visual prognosis vary with the underlying conditions. The incidence of the subtypes varies with the geographic locations. Objective: To study the prevalence of various subtypes of Corneal Dystrophies in corneal button specimens obtained after penetrating keratoplasty in a referral ophthalmic institute and to correlate with the patient’s age and sex. Materials and Methods: Corneal button specimens received in the ocular pathology laboratory over a period of five years were reviewed. Histopathological features of Corneal Dystrophies were studied and subcategorised. Cliniopathological analysis was made. Results: Out of 660 corneal biopsies reviewed, 42 cases were of corneal dystrophy. The patients were between 2 and 71 years of age, with 14 males and 28 females. Macular dystrophy was the most common with 20 cases, followed by Congenital Hereditary Endothelial Dystrophy (CHED) and Fuch’s endothelial dystrophy (FECD), with 7 cases each. Epithelial basement membrane dystrophy, Reis Buckler Dystrophy (RBCD), Granular dystrophy were the other types. Conclusion: Histopathological sub categorisation of various types of Corneal Dystrophies not only helps in understanding the prevalence, but also in predicting the genetic link and prognosis of the disease category. Keywords: Cornea, CHED, Dystrophy, Fuch, Macular.

Purpose of review Ocular surface disease can significantly impact the outcomes of cataract surgery. Recent studies have examined the efficacy of several new dry eye disease (DED) therapies, the extent to which epithelial debridement affects keratometric measurements in epithelial basement membrane dystrophy (EBMD) and Salzmann nodular degeneration (SND), and the predictability of refractive error following combined pterygium and cataract removal. This review aims to incorporate these newer studies in updating and further emphasizing the need for careful management and optimization of common ocular surface conditions prior to cataract surgery. Recent findings Common ocular surface conditions such as DED, EBMD, SND, and pterygium can cause significant irregular astigmatism and higher-order aberrations. Their resolution can substantially alter biometry measurements in preparation for cataract surgery, affecting the final visual outcome. Newer therapies for DED, such as topical lifitegrast and thermal pulsation treatment, can aid in this optimization process. If superficial keratectomy or excisions of lesions on the ocular surface are performed, sufficient healing time is needed to allow the ocular surface to reach stability prior to biometry measurements. Summary Ocular surface optimization is key to successful cataract surgery planning and reaching desired outcomes.

Photorefractive keratectomy (PRK) was performed to treat corneal epithelial basement membrane dystrophy (EBMD) found after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) in a 29-year-old man with previous silent cornea. The patient was diagnosed with post-FS-LASIK EBMD by slitlamp examination and in vivo confocal microscopy (IVCM). Initial treatment with topical lubricants and alcohol soaking was unsuccessful, and the patient continued to have blurred vision and discomfort. The patient underwent a PRK procedure, and the symptoms resolved dramatically; residual refractive errors were also corrected. IVCM revealed a characteristic presentation of EBMD before PRK and normal corneal epithelium after treatment. Patients with asymptomatic EBMD might suffer from recurrent corneal erosions after FS-LASIK. Surface ablation including PRK might lead to successful treatment outcomes, and IVCM might provide helpful information before and after treatment.

To determine the effects of epithelial basement membrane dystrophy (EBMD) and Salzmann nodular degeneration (SND) on optical biometry measurements.Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina, USA.Retrospective case series.Cataractous eyes with EBMD or SND scheduled for superficial keratectomy (SK) or phototherapeutic keratectomy (PTK) had baseline biometry. Repeat biometry was performed 30 days or more postoperatively and compared with baseline. The primary outcome measures were keratometry (K) values, axial length and magnitude, and axis of corneal astigmatism. Secondary outcome measures were the change in intraocular lens (IOL) power, toricity, and axis.In the EBMD group (26 eyes), the mean absolute intersession difference showed an increase in mean K values (P .001) and a change in IOL spherical power predicting a postoperative spherical equivalent (SE) closest to zero (P .001) in 21 of 26 eyes (8 = 0.5 diopter [D]; 9 = 1.0 D; 4 1.0 D). In toric IOL-eligible eyes, the recommended IOL toricity changed for 16 of 24 eyes, with a mean cylinder power change of 1.2 D. In the SND group (13 eyes), the mean absolute intersession difference showed an increase in mean K values (P = .023) and a change in IOL spherical power predicting a postoperative SE closest to zero (P .001) in 11 of 13 eyes (3 = 0.5 D; 3 = 1.0 D; 5 1.0 D). The recommended IOL toricity changed for 10 of 11 eyes (mean cylinder power change 1.5 D).Both EBMD and SND altered K measurements as evidenced by clinically significant changes in keratometry after SK or PTK. These changes affected the spherical and toric IOL power. Appropriate management of EBMD and SND before cataract surgery can yield more reliable biometric data for surgical planning.

Purpose: Treatment of persistent ocular discomfort in patients with Cogan's epithelial basement membrane dystrophy (EBMD) is a challenge for ophthalmologists. This study aimed to determine...

We describe two patients in whom postsurgical refractive error occurred after routine refractive lens exchange cataract surgery with multifocal intraocular lens insertion most likely attributable to the presence of underlying corneal epithelial basement membrane dystrophy (EBMD). In Case 1, there was an unexpected hyperopic postoperative spherical equivalent refractive error of +1.50 diopters and in Case 2, a cylindrical refractive error of 2.75 diopter cylinder. We examine the possible causes of error and discuss potential management strategies to prevent and address these unpredictable postoperative outcomes. The importance of comprehensive and careful ocular surface assessment before cataract or refractive surgery as part of the presurgical workup is reemphasized. EBMD can be subtle and if overlooked, can affect the validity of biometric keratometric measurements preoperatively, resulting in an inaccurate biometry measurement, incorrect IOL selection, and reduced visual performance and patient satisfaction.

In 2015, the first revision of the international classification of corneal dystrophies (IC3D) has been published. According to this latest version of the IC3D the dystrophies of the cornea are divided into · epithelial and subepithelial dystrophies,. · epithelial-stromal TGFBI dystrophies,. · stromal dystrophies, and. · Descemet-membrane and endothelial dystrophies.. This article summarizes the epithelial and subepithelial dystrophies of the cornea, which, according to IC3D are the following: · epithelial basement membrane dystrophy (EBMD),. · epithelial recurrent erosion dystrophy (ERED),. · subepithelial mucinous corneal dystrophy (SMCD),. · Meesmann corneal dystrophy (MECD),. · Lisch epithelial corneal dystrophy (LECD),. · gelatinous drop-like corneal dystrophy (GDLD).. The main problem concerning almost all dystrophies of the corneal epithelium are epithelial defects (erosion) associated with pain, epiphora and red eyes. In addition, all dystrophies of the epithelium tend to relapse.While therapy is usually initiated with topical therapeutics, in the course of the disease invasive procedures like phototherapeutic keratectomy (PTK) (possibly with the administration of mitomycin C) or in severe cases even keratoplasty (preferably as deep anterior lamellar keratoplasty; DALK) have to be used. Due to the origin of the disease in the epithelial stem cells at the limbus, the replacement of these cells can also be discussed.

Purpose To comprehensively review the literature regarding recurrent corneal erosion (RCE) and to present treatment options and recommendations for management. Overview RCE usually presents with sharp, unilateral pain upon awakening, in an eye with an underlying basement membrane dystrophy, prior ocular trauma, stromal dystrophy or degeneration, or prior surgery for refractive errors, cataracts, or corneal transplantation. Making the correct diagnosis requires a careful slit-lamp examination of both eyes coupled with a high degree of suspicion. Several treatments are commonly used for RCE but new therapies have been introduced recently. Conservative treatment consists of antibiotic and preservative-free lubricating drops, with topical cycloplegics and oral analgesics to control pain. Patients who are unresponsive to these therapies may benefit from therapeutic bandage contact lenses (BCL). Newer therapies include oral matrix metalloproteinase (MMP) inhibitors, blood-derived eye drops, amniotic membrane graft application, and judicious application of topical corticosteroids. Once the epithelium is healed, a course of hypertonic saline solution and/or ointment can be used. Surgical procedures may be performed in patients who fail conservative therapy. Punctal occlusion with plugs increases the tear film volume. Epithelial debridement with diamond burr polishing (DBP), anterior stromal puncture (ASP), or alcohol delamination should be considered in selected patients. DBP can be used for patients with basement membrane dystrophies and is the preferred treatment overall due to a low recurrence rate. ASP can be used for erosions outside the central visual axis. Excimer laser phototherapeutic keratectomy is an attractive option in eyes with central RCE since it precisely removes tissue while preserving corneal transparency. In patients with RCE who are also candidates for refractive surgery, photorefractive keratectomy can be considered. Summary Newly introduced therapies for RCE enable therapy to be individualized and lower the recurrence rate.

A 73-year-old man presented with bilateral corneal opacities. Slit-lamp biomicroscopy showed vortex and oval-shaped opacities. In vivo confocal microscopy (IVCM) showed findings characteristic of amiodarone-induced keratopathy along with epithelial basement membrane dystrophy (EBMD). The IVCM findings indicated that the oval-shaped opacities can be present with amiodarone-induced keratopathy in patients with EBMD.

Purpose To report the prevalence of ocular surface dysfunction in patients presenting for cataract surgery evaluation. Setting Duke University Eye Center and Weill Cornell Ophthalmology, single-physician practices. Design Prospective case series. Methods Consecutive patients presenting for cataract surgery evaluation were identified. Patient information including demographics, medical history, slitlamp findings, tear osmolarity, and tear matrix metalloproteinase-9 (MMP-9) levels were recorded. Patients were considered to have ocular surface dysfunction if any of the following outcomes were present: visually significant abnormal corneal surface examination, positive MMP-9 test, or abnormal osmolarity values (>307 mOsm/L or >7 mOsm/L intereye difference). Patient symptoms were recorded using the ocular surface disease index (OSDI) or Symptom Assessment iN Dry Eye questionnaires. Results There were 120 patients (69% women), mean age 69.5 years ± 8.4 (SD). Abnormal osmolarity was found in 68 patients (56.7%), and abnormal MMP-9 in 76 patients (63.3%). Clinical findings showed that 47 patients (39.2%) had positive corneal staining on presentation, 9 patients (7.5%) had epithelial basement membrane dystrophy, and 2 patients (1.6%) had Salzmann nodules. Questionnaire data showed 54 (54.0%) of 100 patients reported symptoms suggestive of ocular surface dysfunction. In the asymptomatic group of 46 patients, 39 (85%) had at least 1 abnormal tear test (osmolarity or MMP-9) and 22 (48%) had both tests abnormal. Overall, 96 (80%) of 120 patients had at least 1 abnormal tear test result suggestive of ocular surface dysfunction and 48 patients (40%) had 2 abnormal results. Conclusions Objective ocular surface dysfunction findings were common among patients presenting for cataract surgery, yet many presented undiagnosed. Clinicians should be aware of this high prevalence and consider screening with tear testing before surgery.

PURPOSEThis case report highlights how epithelial basement membrane dystrophy (EBMD), coupled with dry eye, can contribute to symptoms of unstable vi-sion and discomfort. This report also reviews corneal dystrophies and offers eye care practitioners (ECPs) clinical pearls for identifying key features. CASE REPORTA 62-year-old Caucasian female presented for a dry eye evaluation due to fluctuating vision and longstanding ocular discomfort, despite ocular lubri-cation. Anterior segment examination revealed Meibomian gland dysfunc-tion (MGD), upper lid margin staining (ULMS) and anterior blepharitis. The patient was unaware of a pre-existing EBMD and this lack of knowl-edge contributed to her frustration concerning her unstable vision, which she had solely attributed to her glasses. Management included warm com-presses for MGD and targeted preservative-free artificial tears for ULMS and EBMD. Photographs were essential for educating the patient with respect to the irregularities of the ocular surface and its effect on vision. This provided a deeper understanding of the multifactorial nature of her symptoms.CONCLUSIONUnstable and/or poor vision is among the main reasons why patients con-sult ECPs and it can be difficult to identify contributory factors. This report highlights that additional chair time may be warranted to educate patients on the multifactorial nature of dry eye and the complexities of corneal dys-trophy.

Purpose To comprehensively review the literature regarding recurrent corneal erosion (RCE) and to present treatment options and recommendations for management. Overview RCE usually presents with sharp, unilateral pain upon awakening, in an eye with an underlying basement membrane dystrophy, prior ocular trauma, stromal dystrophy or degeneration, or prior surgery for refractive errors, cataracts, or corneal transplantation. Making the correct diagnosis requires a careful slit-lamp examination of both eyes coupled with a high degree of suspicion. Several treatments are commonly used for RCE but new therapies have been introduced recently. Conservative treatment consists of antibiotic and preservative-free lubricating drops, with topical cycloplegics and oral analgesics to control pain. Patients who are unresponsive to these therapies may benefit from therapeutic bandage contact lenses (BCL). Newer therapies include oral matrix metalloproteinase (MMP) inhibitors, blood-derived eye drops, amniotic membrane graft application, and judicious application of topical corticosteroids. Once the epithelium is healed, a course of hypertonic saline solution and/or ointment can be used. Surgical procedures may be performed in patients who fail conservative therapy. Punctal occlusion with plugs increases the tear film volume. Epithelial debridement with diamond burr polishing (DBP), anterior stromal puncture (ASP), or alcohol delamination should be considered in selected patients. DBP can be used for patients with basement membrane dystrophies and is the preferred treatment overall due to a low recurrence rate. ASP can be used for erosions outside the central visual axis. Excimer laser phototherapeutic keratectomy is an attractive option in eyes with central RCE since it precisely removes tissue while preserving corneal transparency. In patients with RCE who are also candidates for refractive surgery, photorefractive keratectomy can be considered. Summary Newly introduced therapies for RCE enable therapy to be individualized and lower the recurrence rate.

Purpose To investigate the corneal epithelial thickness topography with optical coherence tomography (OCT) and its relationship with vision quality in epithelial basement membrane dystrophy (EBMD). Methods 45 eyes of EBMD patients, 26 eyes of dry eye (DED) patients and 22 eyes of normal subjects were enrolled. All participants were subjected to 9-mm corneal epithelial mapping with OCT and vision quality was assessed with the optical quality analysis system using the objective scatter index (OSI). Central, superior, inferior, minimum, maximum, and standard deviation of epithelium thickness (Irregularity), were analysed and correlations with the OSI were calculated. Results The mean (±SD) central, inferior and maximum epithelial thicknesses of the EBMD patients (respectively, 56.4 (±8.1) μm, 58.9 (±6.4) μm, and 67.1 (±8.3) μm) were thicker compared to DED patients (PPP = 4.4.10−6) and normal subjects (2.1±0.7 μm) (P = 7.6.10−7). The mean OSI was worse in EBMD patients than in DED patients (P = 0.01) and compared to normal subjects (P = 0.02). The OSI correlated with the epithelial thickness irregularity (Spearman coefficient = 0.54; P = 2.65.10−5). Conclusions The OCT pachymetry map demonstrated that EBMD patients had thicker corneal epithelium in the central and inferior region. These changes were correlated with objective measurements of vision quality. This OCT characterisation of the EMBD provides a better understanding of the epithelial behaviour in this dystrophy and its role in vision quality.

Objective To determine the misdiagnosis of ectasia in patients referred for corneal crosslinking and possible topography-guided photorefractive keratectomy (PRK) or intrastromal corneal rings. Setting Bochner Eye Institute, Toronto, Ontario, Canada. Design Retrospective data review. Methods Chart review of consecutive cases referred for corneal crosslinking to determine the number of cases of misdiagnosis of ectasia. Examination findings were reviewed consisting of best-corrected spectacle distance acuity, slit lamp examination, and computerized tomography. Results The study analyzed 1000 consecutive records of patients referred with a presumed diagnosis of keratoconus, pellucid marginal degeneration, and ectasia after laser vision correction that were examined between January 1, 2010 and November 1, 2016. There were 26 eyes without ectasia detected in 20 patients. The etiology of these misdiagnoses was epithelial basement membrane dystrophy (9 eyes), superficial punctate keratitis (7 eyes), amblyopia secondary to high astigmatism (3 eyes), amiodarone keratopathy (2 eyes), corneal warpage from rigid gas permeable lenses (2 eyes), corneal scars (1 eye), and measurement or alignment error with topography (2 eyes). Conclusion Analysis of data detected a misdiagnosis of ectasia in 20 patients (26 eyes), a finding of 2.0% (20 of 1000) of referred cases that did not satisfy the diagnostic criteria of corneal ectasia. These conditions are considered a contraindication to corneal crosslinking and there is usually no benefit to topography-guided PRK or intrastromal corneal rings. It is important that clinicians recognize the clinical findings of these conditions and differentiate from true keratoconus, pellucid marginal degeneration, or ectasia after laser vision correction.

Purpose To determine the efficacy of epithelial debridement and diamond burr polishing (ED + DBP) in managing recurrent corneal erosion (RCE) and visually significant epithelial irregularity associated with epithelial basement membrane dystrophy (VS-EBMD). Methods Retrospective, interventional, consecutive case series of all ED + DBP procedures performed between December 1, 2002, and December 1, 2014. Results ED + DBP was performed in 91 eyes (66 patients) for the management of RCE and VS-EBMD. Sixty percent (55/91) of the procedures were performed for RCE, of which 65% (36/55) were associated with EBMD and 22% (12/55) with previous corneal trauma. Forty-six percent (42/91) of the procedures were performed for VS-EBMD, including 6 eyes with RCE. RCE resolved after treatment in 97% of eyes with >3 months of follow-up (mean, 33.2 months; range, 3.5-137.6 months). Corrected distance visual acuity (CDVA) and mean topographic astigmatism improved significantly in the 36 eyes treated for VS-EBMD with >1 month of follow-up. In none of the 22 eyes treated for VS-EBMD with >3 months of follow-up did EBMD recur (mean, 31.7 months; range, 3.2-137.6 months). Surgically induced subepithelial haze was present on last follow-up in 9.4% (8/85) of eyes with >1 month of follow-up, but was not associated with decreased final CDVA in any patient. Conclusions ED + DBP is effective in producing long-term resolution of RCE in 95% of treated eyes and significant improvement in CDVA, decreased topographic astigmatism, and long-term resolution of VS-EBMD in 100% of treated eyes.

Corneal dystrophies are a rare group of hereditary disorders, that are bilateral, non-inflammatory, and progressive. Clinically, they can be classified based on the anatomic layer of the cornea affected. Refractive surgery and phototherapeutic keratectomy (PTK) can be performed with caution in patients with certain corneal dystrophies, but should be avoided in others. For epithelial basement membrane dystrophy, photorefractive keratectomy (PRK) is the procedure of choice for treatment of refractive error, and PTK may be performed for the treatment of recurrent erosions or irregular astigmatism. PRK and laser-assisted in situ keratomileusis (LASIK) have been associated with exacerbation of combined granular-lattice corneal dystrophy. LASIK and PRK appear to be safe in mild forms of posterior polymorphous corneal dystrophy, whereas LASIK should be avoided in Fuchs dystrophy. The safety of refractive surgery and PTK in the remainder of epithelial, Bowman layer, and stromal dystrophies has yet to be established.

Purpose: To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs' endothelial corneal dystrophy (FECD). Methods: A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing. Results: Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman's layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1. Conclusion: This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy.

Rationale: The etiology of anterior corneal opacities and the effect of debridement cannot be determined by biomicroscopy. Optical coherence tomography (OCT) helps identify the character and depth of these lesions. Patient concerns: A 45-year-old female complained of progressive blurred vision for a long time. Slit lamp biomicroscopy showed irregular, faint scar-like opacity of anterior cornea in her both eyes. Pentacam Scheimpflug camera tomography showed irregular astigmatism of anterior corneal surface. Anterior segment spectral-domain OCT revealed thickened, hyper-reflective linings, and scattered lesions, mainly in the epithelial layer. Diagnoses: Epithelial basement membrane dystrophy (EBMD). Intervention: Epithelial debridement and bandage lenses. Outcomes: The cornea became clear and the vision improved soon after debridement. The pathology showed thickened aberrant basement membrane extending into mid-epithelial layer, with microcyst-like lesions also noted. Lessons: OCT defines the depth of lesions and helps diagnosis and management of EBMD.

A 48-year-old woman with no significant past history underwent bilateral simultaneous laser in situ keratomileusis for correction of her myopia. On the tenth postoperative day, the patient complained of visual decrease and photophobia. Slit lamp exam showed corneal epithelial irregularities. Confocal microscopy was performed and revealed a characteristic appearance of epithelial basement membrane dystrophy (EBMD). The patient was successfully treated with artificial tears and autologous serum eyedrops. EBMD may be missed before LASIK surgery, even after a careful pre-operative examination. Exacerbation of EBMD after LASIK surgery is rare. It should be considered when unexplained corneal epithelial defects or irregularities occur following LASIK. Confocal microscopy is very useful to confirm the diagnosis.

Purpose To describe the corneal findings in posterior polymorphous corneal dystrophy (PPCD) as imaged with laser scanning in vivo confocal microscopy (IVCM). Methods IVCM images of 7 subjects with PPCD who had typical slit-lamp biomicroscopic findings of endothelial vesicular, band, and/or placoid lesions were evaluated. Results Five women and 2 men aged 7 to 64 years were included in this study. Laser scanning IVCM (Heidelberg Retina Tomograph II, Rostock Cornea Module) revealed hyporeflective, round, vesicular lesions with diameters ranging between 20 and 200 µm in 3 subjects, combined vesicular and curvilinear hyperreflective band-like lesions in 3 subjects, and combined vesicular and placoid hyperreflective lesions in 1 subject at the level of Descemet membrane (DM), endothelial cell layer, and posterior stroma adjacent to DM. One subject had coassociated epithelial basement membrane dystrophy. Additional findings included posterior stromal keratocytes with elongated spindle-like nucleus, giant and nucleated endothelial cells, endothelial deposits, and guttae-like dark spots. The mean endothelial cell density was 1485.7 ± 486.3 cells per square millimeter (range, 990-2365 cells/mm). The mean central corneal thickness was 585.3 ± 37.17 μm (range, 534-643 μm). Conclusions Laser scanning IVCM is able to highlight the characteristic microstructural alterations at the level of endothelium and DM in the setting of PPCD and may have diagnostic utility in equivocal cases with borderline biomicroscopic findings. The possible association of PPCD with epithelial basement membrane dystrophy warrants further investigation.

Background: Epithelial basement membrane dystrophy (EBMD) is by far the most common corneal dystrophy. In this study, we used a newly developed method of immunofluorescence staining and imaging to study the entire corneal nerve architecture of a donor with unilateral EBMD. Method: Two fresh eyes from a 56-year-old male donor were obtained; the right eye of the donor was diagnosed with EBMD and the left was normal. After slit lamp examination, the corneas were immunostained with anti-β-tubulin III antibody. Images were recorded by a fluorescent microscope equipped with a Photometrics digital camera using MetaVue imaging software. Results: The left cornea appeared normal as observed by slit lamp and stereomicroscope, but the right eye had numerous irregular geographic patches in the basement membrane. Immunofluorescence showed no difference in the stromal nerve distribution between the 2 eyes, but there were areas without innervations in the EBMD cornea. Subbasal nerve fibers also showed tortuous courses and fewer divisions. There was a significant decrease in the density of subbasal nerve fibers and the number of terminals in the right eye. Conclusion: We show for the first time detailed nerve architecture in an EBMD cornea. Our results suggest that EBMD-induced abnormalities of basement membrane altered epithelial nerve architecture and decreased nerve density, contributing to the pathology of the disease.

Wen-Shin Lee, Carson K Lam, Edward E Manche Department of Ophthalmology, Stanford University, Stanford, CA, USA Purpose: The purpose of this study was to evaluate the long-term efficacy of phototherapeutic keratectomy (PTK) in treating epithelial basement membrane dystrophy (EBMD).Methods: Preoperative and postoperative records were reviewed for 58 eyes of 51 patients with >3months follow-up (range 3−170months) treated for EBMD with PTK after failure of conservative medical treatment at Byers Eye Institute of Stanford University. Symptoms, clinical findings, and corrected distance visual acuity (CDVA) were assessed. The primary outcome measure was symptomatic recurrence as measured by erosions or visual complaints >3months after successful PTK.Results: For eyes with visual disturbances (n=30), preoperative CDVA was ~20/32 (0.24 LogMAR, SD 0.21) and postoperative CDVA was ~20/25 (0.07 LogMAR, SD 0.12; P

Purpose: The majority of anterior corneal dystrophies are caused by dominant mutations in TGFBI (transforming growth factor β-induced) collectively known as the epithelial-stromal TGFBI dystrophies. Most cases of epithelial basement membrane dystrophy (EBMD) are thought to result from a degenerative (nongenetic) process; however, a minority of cases are associated with specific TGFBI mutations. We evaluated the spectrum of TGFBI mutations and associated phenotypes in a United Kingdom cohort with typical epithelial-stromal TGFBI dystrophies and an EBMD cohort. Methods: We recruited 68 probands with a clinical diagnosis of epithelial-stromal TGFBI dystrophy and 23 probands with bilateral EBMD. DNA was extracted from peripheral leukocytes, and TGFBI was bi-directly Sanger sequenced. Results: Nine TGFBI mutations were identified. The most common occurred at the mutation hot-spot residues R124 and R555 in 61 probands; these individuals had a genotype-phenotype correlation consistent with prior reports. Four probands with lattice corneal dystrophy carried a mutation in exon 14: p.(A620D), p.(V625D), and p.(H626R). We identified a p.(G623D) mutation in five probands, including two probands from the EBMD cohort. These subjects typically had an onset of severe recurrent corneal epithelial erosion in the fourth decade with mild diffuse or geographic subepithelial corneal opacities and only small anterior stromal lattice structures in older individuals. Symptoms of painful epithelial erosion improved markedly following phototherapeutic keratectomy. Conclusions: There was a strong correlation between genotype and phenotype for the majority of TGFBI mutations. In this cohort, the p.(G623D) mutation caused a greater proportion of TGFBI-associated disease than anticipated, associated with variable phenotypes including individuals diagnosed with EBMD.

Akira Kobayashi, Hideaki Yokogawa, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanBackground: The purpose of this study was to investigate pathological changes of the corneal cell layer in patients with map-dot-fingerprint (epithelial basement membrane) dystrophy by in vivo laser corneal confocal microscopy.Methods: Two patients were evaluated using a cornea-specific in vivo laser scanning confocal microscope (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM). The affected corneal areas of both patients were examined. Image analysis was performed to identify corneal epithelial and stromal deposits correlated with this dystrophy.Results: Variously shaped (linear, multilaminar, curvilinear, ring-shape, geographic) highly reflective materials were observed in the “map” area, mainly in the basal epithelial cell layer. In “fingerprint” lesions, multiple linear and curvilinear hyporeflective lines were observed. Additionally, in the affected corneas, infiltration of possible Langerhans cells and other inflammatory cells was observed as highly reflective Langerhans cell-like or dot images. Finally, needle-shaped materials were observed in one patient.Conclusion: HRT 2-RCM laser confocal microscopy is capable of identifying corneal microstructural changes related to map-dot-fingerprint corneal dystrophy in vivo. The technique may be useful in elucidating the pathogenesis and natural course of map-dot-fingerprint corneal dystrophy and other similar basement membrane abnormalities.Keywords: cornea, confocal microscopy, map-dot-fingerprint dystrophy, epithelial basement membrane dystrophy, Heidelberg Retina Tomograph 2 Rostock Cornea Module (HRT 2-RCM)

Purpose To ascertain the effects of aging on corneal morphology and to illustrate the morphologic diversity of the different layers in the normal cornea as seen by in vivo confocal microscopy (IVCM). Design Observational cross-sectional study. Participants A total of 150 healthy subjects, evenly distributed over 5 age categories, comprising 75 men and 75 women. Methods Both transparent corneas (n = 300) of all subjects were examined in duplicate by white light IVCM (Confoscan 4, NIDEK Technologies, Albignasego, Padova, Italy). After reviewing the IVCM examinations for morphologic variations of the corneal layers, we selected the 8 most common features to illustrate the morphologic diversity. Subsequently, all 600 IVCM examinations were assessed for the presence of these features. We used binary logistic regression analyses to assess the age-relatedness of each feature. Main Outcome Measures Age distribution of bright superficial epithelial cells, dendriform cells, alterations characteristic of epithelial basement membrane dystrophy (EBMD), tortuous stromal nerves, stromal microdots in the anterior stroma, folds in the posterior stroma, opacification of Descemet's membrane, and corneal guttae. Results Four features were found characteristic of the aging cornea: stromal microdots in the anterior stroma ( P P P P P = 0.09). Other features, such as bright superficial epithelial cells (n = 38, 13%), dendriform cells (n = 42, 14%), and tortuous stromal nerves (n = 115, 38%), were age-independent. We also found a novel phenotype of corneal endothelium in 4 normal eyes of 2 subjects, which we coined "salt and pepper endothelium." We could not establish whether this novel phenotype represented a morphologic variant of normal endothelium, an early stage of a known corneal endothelial disorder, or a completely new disease entity. Conclusions Knowledge of the common morphologic variations of the corneal layers and the effects of aging on corneal morphology as seen by IVCM increases our understanding of corneal degenerative disorders and is essential to detect corneal pathology. Our finding of a novel phenotype of corneal endothelium emphasizes the morphologic diversity of this optically transparent tissue. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective To evaluate the outcome of phototherapeutic keratectomy (PTK) treatment of epithelial basement membrane dystrophy (EBMD) patients and to examine clinical and morphologic signs of recurrent dystrophy. Design Cross-sectional, clinic-based study. Participants Fifty-two eyes of 39 patients diagnosed with EBMD who underwent PTK between 2001 and 2008. Methods Preoperative symptoms, best spectacle-corrected visual acuity (BSCVA), and refraction data were collected. At follow-up, refraction and BSCVA were measured, symptoms were noted, and slit-lamp biomicroscopy and in vivo confocal microscopy (IVCM) were performed. Main Outcome Measures Best spectacle-corrected visual acuity and signs of recurrent EBMD based on symptoms and morphologic features. An assessment of EBMD severity after PTK additionally was considered. Results Mean follow-up time was 43 months (range, 7–100 months). After PTK, BSCVA remained unchanged or improved in 49 (98%) of 51 eyes. Twenty-four (46%) of 52 eyes had recurrence of some form, and recurrence was correlated positively with postoperative time ( P Conclusions Although PTK is an effective method of alleviating the clinical symptoms of EBMD, the dystrophy can recur with time. The relationship between the postoperative development of clinical symptoms and the corneal morphologic features is complex and requires further investigation. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To describe a patient with a history of epithelial basement membrane dystrophy who developed symptomatic corneal verticillata after vandetanib therapy for anaplastic astrocytoma.Retrospective interventional case report.A 48-year-old female patient with a history of anaplastic astrocytoma status post resection, external beam radiation, and chemotherapy presented with glare symptoms, decreased contrast sensitivity, and increased lacrimation after approximately 12 months of therapy with the anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor 2 protein tyrosine kinase inhibitor, vandetanib. Ophthalmic examination revealed diffuse corneal verticillata and fine subepithelial opacities. Schirmer 1 testing was normal bilaterally. Therapy with carboxymethylcellulose, 5% sodium chloride ointment, and a decrease in the dose of vandetanib led to an improvement in the patient's ophthalmic symptoms despite persistence of the corneal findings. The patient remained under surveillance for tumor recurrence.Vandetanib (ZD6474), a protein tyrosine kinase inhibitor with dual anti-EGFR and anti-vascular endothelial growth factor receptor 2 action, may have contributed to the formation of corneal verticillata in our patient. Inhibition of EGFR, which is involved with corneal epithelial cell migration and wound healing, may play a role in the pathogenesis underlying corneal vortex keratopathy and ocular surface conditions with significant epithelial turnover.

PURPOSE To report a rare case of bilateral and symmetric Meesmann corneal dystrophy concurrent with bilateral epithelial basement membrane dystrophy and bilateral but asymmetric posterior polymorphous corneal dystrophy in a patient of Armenian origin. METHODS Complete ophthalmologic examination was performed on a 6-year-old boy from Armenia who was diagnosed with bilateral symmetric Meesmann corneal dystrophy combined with bilateral epithelial basement membrane dystrophy and bilateral but asymmetric posterior polymorphous corneal dystrophy. This case was observed and treated for 24 years. RESULTS On slit-lamp biomicroscopy, the patient showed bilateral multiple intraepithelial cystic lesions, bilateral irregularly shaped grayish-white opacities in the superficial corneal epithelium, and bilateral but asymmetric transparent vesicles surrounded by gray halos at the level of the Descemet membrane and the endothelium. CONCLUSIONS This case is reported because of the unusual occurrence of Meesmann corneal dystrophy with other corneal dystrophies.

Purpose Autosomal dominant mutations in TGFBI cause a range of clinically distinct corneal dystrophies. We investigated the TGFBI mutation spectrum in our cohort and correlated genotype with phenotype. Methods TGFBI exons 4, 11, 12, 13, 14 and 16 were Sanger sequenced in 59 unrelated probands attending Moorfields Eye Hospital with a diagnosis of a potential TGBFI-associated corneal dystrophy. Results The majority of individuals, 86%, carried a mutation at one of the two known hotspot residues for TGFBI-associated corneal dystrophies: Arg-124 and Arg-555. Mutations affecting either of these residues demonstrated genotype-phenotype correlation. A c.1868G>A; p.(Gly623Asp) mutation was identified in five unrelated probands; one with a clinical diagnosis of lattice corneal dystrophy, two with a Bowman's layer dystrophy (Reis-Bϋcklers or Thiel-Behnke corneal dystrophy) and two with epithelial basement membrane dystrophy (EBMD). The clinical variability associated with this mutation indicates that other genetic or environmental factors can influence phenotypic expression. Conclusions This is the first time the c.1868G>A; p.(Gly623Asp) mutation has been associated with EBMD, although other mutations in TGFBI have previously been identified in a small number of EBMD patients. These results demonstrate that the c.1868G>A; p.(Gly623Asp) mutation is responsible for a significant proportion of the disease burden for TGFBI-associated corneal dystrophies in the UK and highlights the need for patients with EBMD to be screened for mutations in TGFBI.

Purpose.To compare anterior eye segment measurements and morphology obtained with two optical coherence tomography systems (TD OCT, SS OCT) in eyes with corneal dystrophies (CDs).Methods. Fifty healthy volunteers (50 eyes) and 54 patients (96 eyes) diagnosed with CD (epithelial basement membrane dystrophy, EBMD = 12 eyes; Thiel-Behnke CD = 6 eyes; lattice CD TGFBI type = 15 eyes; granular CD type 1 = 7 eyes, granular CD type 2 = 2 eyes; macular CD = 23 eyes; and Fuchs endothelial CD = 31 eyes) were recruited for the study. Automated and manual central corneal thickness (aCCT, mCCT), anterior chamber depth (ACD), and nasal and temporal trabecular iris angle (nTIA, tTIA) were measured and compared with Bland-Altman plots.Results.Good agreement between the TD and SS OCT measurements was demonstrated for mCCT and aCCT in normal individuals and for mCCT in the CDs group. The ACD, nTIA, and tTIA measurements differed significantly in both groups. TBCD, LCD, and FECD caused increased CCT. MCD caused significant corneal thinning. FECD affected all analyzed parameters.Conclusions.Better agreement between SS OCT and TD OCT measurements was demonstrated in normal individuals compared to the CDs group. OCT provides comprehensive corneal deposits analysis and demonstrates the association of CD with CCT, ACD, and TIA measurements.

Purpose To describe corneal changes in patients with epithelial basement membrane dystrophy (EBMD) using a new in vivo confocal microscope. Design Observational case series. Methods A retrospective chart review of 22 consecutive patients with EBMD at the Quinze-Vingts National Ophthalmology Hospital from April 2004 to March 2005 was conducted. Gender, age, history of painful episodes suggestive of recurrent erosions, best-corrected visual acuity, slit lamp findings, and in vivo confocal microscopy images were analyzed. Results There were 8 male (36.4%) and 14 female (63.6%) subjects. Eighteen patients (81.2%) had a history of recurrent erosions in 1 or in both eyes. In 37 eyes of 19 patients (86.4%), map and/or dot and/or fingerprint changes were observed biomicroscopically. In 3 patients (13.6%) with recurrent erosions, the cornea had a normal structure on slit lamp examination and the diagnosis of EBMD was made after in vivo confocal microscopy examination. Four patients (18%), despite basement membrane abnormalities, reported no corneal symptoms suggesting recurrent erosions. In vivo confocal microscopy images showed that all patients had an abnormal epithelial basement membrane protruding into the corneal epithelium, epithelial cell abnormalities, and microcysts. No abnormalities were observed in superficial epithelial cells or the stroma. Conclusion Epithelial basement membrane dystrophy is characterized by an abnormal basement membrane protruding toward the epithelium and epithelial microcysts. In vivo confocal microscopy using the HRT II Rostock Cornea Module provides better resolution and therefore outlines distinctively in vivo microstructural characteristics of EBMD. It assists in the diagnosis of EBMD in patients suffering from recurrent erosion syndrome, particularly in patients with no corneal change visible biomicroscopically.