Zone 1 trauma: wound dehiscence compared to primary trauma.

PURPOSE: The study aims to assess if Zone 1 globe injuries hold a favorable prognosis for all situations, including wound dehiscence, or just primary traumatic injuries. METHODS: Retrospective cross-sectional chart review of patients who underwent open globe repair from 1/1/2019 to 12/1/2020 at an urban hospital setting was evaluated for final visual outcomes, associated ocular pathology, long-term complications, and need for further surgeries. RESULTS: Fifty-eight eyes were identified-38 primary trauma and 20 dehisced wounds (11 penetrating keratoplasties, five clear corneal incisions, one laceration, one extracapsular cataract extraction, one radial keratotomy, and one tectonic graft). Dehisced wounds had more posterior segment pathology vs primary trauma, i.e., hemorrhagic choroidal, vitreous hemorrhage, retinal detachment, choroidal effusion (all 20% vs 2.63%, 5.26%, 5.26%, and 0%, respectively), vitreous prolapse (20% vs 2.63%), and uveal prolapse (80% vs 36.84%). Dehisced wounds had more traumatic aphakia (40% vs 0%) and dislocated lenses (15% vs 0%). Primary trauma was more likely to have traumatic cataracts (55.26% vs 10%) or no lens changes (44.74% vs 25%). About 10% dehisced wounds required enucleation (0% primary trauma). Cataract/secondary intraocular lens surgery was performed in 34% of the primary traumas (10% in dehisced wounds). Primary traumas achieved 20/40 vision or better in 44.74% (10% dehisced wounds). About 7.89% of patients with wound dehiscence ended with no light perception (none in primary trauma). CONCLUSION: Zone 1 open globe injuries due to wound dehiscence may exhibit worse prognosis compared to primary trauma open globe injury. More important than the zone of injury may be the source.

Interspecialty Opioid Prescribing Patterns in Ophthalmology Following Declaration of a Public Health Emergency.

Purpose: Previous literature has investigated opioid prescription trends in ophthalmology at large, however, little has been done looking at differences between subspecialties. We evaluate if significant trends exist among subspecialties in opioid prescribing patterns. This study aims to illuminate potential over-usage of opioids in ophthalmology that could compromise patient quality of life. Methods: Medicare data and "National Plan and Provider Enumeration System (NPPES) Downloadable File" were queried for cases of ophthalmologists with nonsuppressed opioid prescription data from 2014 to 2019. Ophthalmologists with no subspecialty code or missing regional, gender, degree, or graduation information were excluded. Chi-squared analysis, analysis of variance, t-tests, and multivariate logistic regression were utilized. Results: Five thousand one hundred forty-three physician records were included in analysis, 450 of which were by cornea subspecialists. Most cornea cases were male, graduated before 2005, and practiced in the South. All subspecialties had a significantly increased likelihood of making opioid claims and higher prescription rates compared with cornea (P < 0.050) besides glaucoma (P = 0.357). Only oculoplastics had significantly increased likelihood of greater total supply of opioids compared with cornea (odds ratio [OR] = 22.195, 95% confidence interval [CI] = 12.209-40.350, P < 0.001), while pediatrics (OR = 4.036, 95% CI = 1.377-11.831, P = 0.011) and neuro-ophthalmology (OR = 4.158, 95% CI = 1.237-13.975, P = 0.021) in addition to oculoplastics (OR = 64.380, 95% CI = 26.306-157.560, P < 0.001) were predicted to have significantly greater opioid beneficiaries. Males, the South/Midwest, and graduating before 2005, all were generally associated with increased likelihood of greater total opioid claims, supply, beneficiaries, and prescription rate (P < 0.050). Conclusion: Subspecialty, demographic, chronological, and regional trends exist for opioid prescribing patterns in ophthalmology.

Effect of simulated cataract on the accuracy of artificial intelligence in detecting diabetic retinopathy in color fundus photos.

PURPOSE: Artificial intelligence (AI) is often trained on images without ocular co-morbidities, limiting its generalizability. This study aims to evaluate the accuracy of a convolutional neural network (CNN) applied to color fundus photos (CFPs) with simulated cataracts (SCs) in detecting diabetic retinopathy (DR). METHODS: A database of 3662 CFPs (from Asia Pacific Tele-Ophthalmology Society (APTOS) 2019) was used. Using transfer learning, a CNN was trained to classify the training images as either DR or non-DR. The CNN was then applied to classify the testing images after an SC was applied, using varying degrees of Gaussian blur. RESULTS: Accuracy without SC was 97.0%, sensitivity (Sn) 95.7%, specificity (Sp) 98.3%. For mild SC, accuracy was 93.1%, Sn 91.8%, Sp 94.3%. For moderate SC, accuracy was 62.8%, Sn 31.4%, Sp 95.2%. For severe SC, accuracy was 53.5%, Sn 11.8%, Sp 96.5%. CONCLUSION: SCs significantly impaired AI accuracy. To prepare AI for clinical use, cataracts and other real-world clinical challenges affecting image quality must be accounted for.

Antibody-Drug Conjugates and Ocular Toxicity.

Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents for the purpose of treating cancers that often have relapsed or failed first- and second-line treatments. ADCs are composed of extremely potent cytotoxins with a variety of side effects, one of the most significant being ocular toxicity. The available literature describes these toxicities as varying in severity and in incidence, although with disparate methods of evaluation and management. Some of the most common toxicities include microcyst-like epithelial keratopathy and dry eye. We discuss proposed mechanisms of ocular toxicity and describe the reports that mention these toxicities. We focus on ADCs with the most published literature and the most significant effects on ocular tissue. We propose areas for further investigation and possible ideas of future management. We provide a comprehensive look at the reports of ADCs in current literature to better inform clinicians on an expanding drug class.

Comparative Analysis of Alternative Calcium Chelators for the Treatment of Calcific Band Keratopathy.

PURPOSE: In this study, we compared clinically relevant biochemical properties of each chelator for pH, osmolarity, and calcium chelation potential. METHODS: In total, 0.2 M K 2 EDTA and K 3 EDTA (BD vacutainer tubes by Becton, Dickinson and Company) and Na 2 EDTA (Sigma Aldrich) solutions were made. The pH of each solution was measured (Mettler Toledo pH meter), and the theoretical osmolarity was calculated. Next, we determined the calcium chelation potential of each EDTA salt by titrating it with 10 µmol of calcium hydroxyapatite or CaCl 2 containing Patton-Reeder colorimetric indicator. Statistical significance was analyzed using analysis of variance. RESULTS: The 0.2 M solutions of Na 2 EDTA, K 2 EDTA, and K 3 EDTA have pH values of 4.43, 5.71, and 9.191 and theoretical osmolarities of 600, 600, and 800 mOsm/L, respectively. Calcium chelation ability was similar among all 3 solutions: 0.94 to 0.98 mol of EDTA was needed to fully chelate 1 mol calcium ions of CaCl 2 ( P = 0.296), 0.100 to 0.108 mol of EDTA for 1 mol calcium ions of the hydroxyapatite aqueous suspension ( P = 0.296), and 0.992 to 0.996 mol for 1 mol calcium ions of hydroxyapatite in acidic solution ( P = 0.178). Compared with the clinical standard of 3% (30 mg/mL) Na 2 EDTA, approximately 3.3% (33 mg/mL) K 2 EDTA and 3.6% (36 mg/mL) K 3 EDTA are needed to chelate an equivalent amount of calcium. CONCLUSIONS: In this article, we provide clinically relevant biochemical properties of 2 alternatives to Na 2 EDTA and demonstrate comparable calcium chelation ability among all 3 solutions. In situations where sterile sources of Na 2 EDTA are unavailable, potassium EDTA may provide a convenient and equally effective method of treatment for band keratopathy.

Vitamin A Deficiency Screening in Patients With Chronic Alcohol-Associated Liver Disease: Implications for Liver Transplant Candidates.

Chronic liver pathologies may lead to vitamin A deficiency (VAD) through impairment of vitamin A absorption, storage, and distribution. VAD can contribute to ocular pathologies, and in the article, we present 2 patients with alcohol-associated cirrhosis admitted for liver transplant presenting with nonhealing central corneal epithelial defects in the eye without other known ocular pathologies. Low serum vitamin A levels were detected in both patients. Vitamin A supplementation eventually helped corneal epithelial healing within days/weeks. We suggest that VAD be screened for in all liver transplant candidates even before ocular symptoms present. This may prevent more severe VAD ocular sequelae.

Female authorship trends and the effect of COVID-19 on cataract and refractive surgery literature.

PURPOSE: To evaluate whether gender barriers persist specifically in the cataract and refractive surgery (CRS) literature. In addition, no literature exists investigating the long-term effect of COVID-19 on female authorship in ophthalmology past 2020. SETTING: Scopus 2015 to 2022. DESIGN: Retrospective data review. METHODS: Articles published in the Journal of Refractive Surgery and the Journal of Cataract & Refractive Surgery were recorded from January 2015 to February 2022 from Scopus. Articles with only 1 author or where gender could not be identified were excluded. The first author (FA) gender, senior author (SA) gender, affiliated country, type of literature, and number of citations were collected. Pearson chi-squared tests with phi coefficients and multivariate logistic regression were performed. RESULTS: 3153 articles were included in analysis. There were 910 works with female FAs and 648 with female SAs. Gender did not predict publishing in one journal over the other (P > .050). Women made up less than 30% of authorship of all types of literature, except for prospective/observational studies as FA (31.3%). Compared with before 2020, female FAs from 2020 onward were associated with increased retrospective analysis (phi = 0.072, P = .030) and letters/editorials (phi = 0.134, P < .001) but decreased case reports (phi = 0.087, P = .009) and "others" (phi = -0.164, P < .001). Similar associations were observed for female SAs. Females were more likely to publish in Asian countries. Female SAs predicted an increased likelihood of female FAs (odds ratio, 1.401, 95% CI, 1.165-1.684, P < .001). CONCLUSIONS: Gender disparities exist in authorship of the CRS literature. COVID-19 has altered the types of literature published by women, but men still publish most of all types of CRS research.

Povidone-Iodine Adverse Effects and Alternatives for Ocular Procedures.

Purpose: Povidone-iodine (PVI), also known as Betadine, is a widely used antiseptic agent used in several fields of medicine. In ophthalmology, it is applied as a preoperative antiseptic to prevent infectious complications that can result from surgical procedures. PVI's safety and efficacy have been extensively studied and represented in the literature; however, the incidence of adverse effects has been reported in conjunction. The aim of this paper is to compile information regarding PVIs use, safety profile, adverse effects, and possible alternatives through a review of the existing literature. Methods: Literature was compiled utilizing the database PubMed and Google Scholar using specified keywords with a total of 86 reviewed articles, after excluding search results that did not meet the inclusion criteria. Results: While the allergic potential to PVI is a highly contested topic, there are several nonallergic adverse effects of PVI that should not be overlooked. These effects include chemical burn, cytotoxic effects, and general patient discomfort. In light of these adverse effects, alternatives to PVI may be considered. However, there has been little research identifying feasible alternatives in preoperative intraocular procedures. Alternatives including chlorhexidine, polyhexamethylene biguanide (polyhexanide), and octenidine were identified as potential substitutes for PVI. Conclusions: Further study is needed to provide robust evidence regarding the efficacy profiles of these alternatives in comparison with PVI and to demonstrate comparable tolerance to PVI in intraocular procedures.

Association between obesity and age-related cataract: an updated systematic review and dose-response meta-analysis of prospective cohort studies.

Objective: There are inconsistent findings on the association between obesity and age-related cataract (ARC). This systematic review was done to summarize available findings on the association between obesity [defined by body mass index (BMI)] and ARC by performing a dose-response meta-analysis on eligible prospective cohort studies. Methods: We performed a systematic search in PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until June 2022 to identify eligible publications. Results: In total, 16 studies with a total sample size of 1,607,125 participants were included. Among all of these studies, there were 103,897 cases of ARC. In the follow-up periods ranging between 4 and 28 years, 4,870 cases of nuclear cataract, 1,611 cases of cortical cataract, and 1,603 cases of posterior subcapsular cataracts (PSC) were detected. By comparing the highest and lowest categories of BMI, we found that higher BMI was associated with an increased risk of ARC (RR: 1.18, 95% CI: 1.09-1.28) and PSC (RR: 1.44, 95% CI: 1.08-1.90). In the dose-response analysis, each 5 kg/m2 increase in BMI was associated with a 6 and 27% increased risk of ARC (RR: 1.06, 95% CI: 1.01-1.12) and PSC (RR: 1.27, 95% CI: 1.14-1.41), respectively. In addition, we found a positive association for cortical cataract among high-quality studies, in which higher BMI was associated with a 20% increased risk of cortical cataract (RR: 1.20, 95% CI: 1.02-1.42). In terms of nuclear cataract, we found no significant association either in the comparison between the highest and lowest categories of BMI or in the dose-response meta-analysis. Conclusion: Obesity (defined by BMI) was associated with an increased risk of ARC, PSC, and cortical cataract in adults. However, such a positive association was not seen for nuclear cataract. PROSPERO registration: CRD42022357132.

Updates in diagnostics, treatments, and correlations between oral and ocular manifestations of Sjogren's syndrome.

Sjogren's syndrome (SS) is characterized as an autoimmune disorder targeting secretory glands, including the lacrimal and salivary glands, causing dry eye and dry mouth predominantly in women over the age of 40. In this review, we summarize recent advancements in SS diagnostics, treatments, and our understanding of correlations between oral and ocular manifestations of SS. Google Scholar and PubMed databases were utilized to search peer-reviewed papers since 2016 on SS diagnosis, treatment, and correlations between oral and ocular manifestations. For diagnostics, we discuss the updated SS classification criteria by the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR), new biomarkers, and compare studies of current diagnostic methods with alternative technologies. For treatments, we discuss topical, systemic, and surgical treatment developments in the management of oral and ocular symptoms of SS as there is still no cure for the disorder. Finally, we report studies that directly suggest correlations between the ocular surface disease and oral disease in SS, as well as shared abnormalities in the microbiome and cytokine expression that may be correlated. We conclude by stating limitations to our review as well as paths moving forward. Elucidating correlations between oral and ocular manifestations may be the key to furthering our understanding of SS pathogenesis as well as defining new standards for diagnosis and treatment.

Pterygium Recurrence Rates in the Hispanic Population in the Northeastern United States.

PURPOSE: To determine the rate and factors affecting pterygium recurrence in the Hispanic population of the Northeastern United States, based on patient demographic information. METHODS: In this retrospective cross-sectional study, data were collected on ethnically Hispanic patients from 2013 to 2018 who had primary single-headed pterygia excision and conjunctival autograft, with the minimum of 4-month follow-up time. This study was conducted in an academic institution in the Northeastern United States, with all patients being from the surrounding community. RESULTS: In 168 Hispanic patients with confirmed primary single-headed pterygium, most pterygia occurred nasally (161/168). The average age of presentation was 46.3 ± 12.0 years (range, 23-77 years). There were 22 recurrences (13.1%), occurring at an average of 3.0 ± 1.6 months (1-8 months). This cohort demonstrated a unimodal recurrence distribution. Age is significantly inversely correlated with the incidence of recurrence (r = -0.219, P = 0.004), but not with the size of the recurrent pterygia (r = -0.112, P = 0.621). There was no significant difference between recurrence based on gender (P = 0.265), location (P = 0.824), or laterality (right or left eye) (P = 0.213). Mean corrected visual acuity improved from 20/40 to 20/32 after pterygium excision (P < 0.001). Cox regression analysis for age groups shows the risk of recurrence for patients aged 20-29 is 11.4-time that of patients aged 50 and above (P < 0.001). CONCLUSIONS: Recurrence occurred unimodally at around 3 months postoperatively. Younger patients are significantly more susceptible to recurrence. Future studies may seek to determine the incidence of pterygia and their recurrence patterns in relation to occupations and sun exposure time in a geographic area.

A Case of Peripheral Ulcerative Keratitis Associated with Autoimmune Hepatitis.

PURPOSE: To describe a case of peripheral ulcerative keratitis in the setting of autoimmune hepatitis and possible overlap syndrome with primary sclerosing cholangitis. CASE REPORT: A 48-year-old African American female with autoimmune hepatitis with possible overlap syndrome with primary sclerosing cholangitis presented with tearing, irritation, and injection of the left eye that was determined to be peripheral ulcerative keratitis. The patient was treated with topical and systemic steroids, immunosuppressant drugs (azathioprine and mycophenolate mofetil), a biologic (rituximab), and surgery (conjunctival resection), and the peripheral ulcerative keratitis epithelialized but ultimately led to corneal perforation. CONCLUSION: In this unique case, a patient with peripheral ulcerative keratitis who underwent treatment ultimately had a corneal perforation. This case may suggest a possible relationship between autoimmune hepatitis and peripheral ulcerative keratitis.

Corneal Nerve and Epithelial Cell Alterations in Corneal Allodynia: An In Vivo Confocal Microscopy Case Series.

PURPOSE: To investigate morphological changes of the corneal epithelium and subbasal nerves in patients with corneal allodynia using in vivo confocal microscopy (IVCM). DESIGN: Case-control study of patients with corneal allodynia and healthy controls. METHODS: Ten eyes of six patients were diagnosed with corneal allodynia at a single center and compared to fifteen healthy eyes. IVCM of the central cornea was performed on all subjects and controls. Images were retrospectively analyzed numbers of total corneal subbasal nerves, main trunks and branches, total nerve length and density, nerve branching, and tortuosity, superficial and basal epithelial cell densities, and superficial epithelial cell size. RESULTS: Corneal allodynia was seen in patients with dry eye disease, recurrent corneal erosion syndrome, exposure to ultraviolet radiation, and Accutane use. Compared to controls, patients with corneal allodynia had a significant decrease in the total numbers of subbasal nerves (P=.014), nerve branches (P=.006), total nerve length (P=.0029), total nerve density (P=.0029) and superficial and basal epithelial cell densities (P=.0004, P=.0036) with an increase in superficial epithelial cell size (P=.016). There were no statistically significant differences in the number of subbasal nerve main trunks (P=.09), nerve branching (P=.21), and nerve tortuosity (P=.05). CONCLUSIONS: Corneal IVCM enables near-histological visualization and quantification of the cellular and neural changes in corneal allodynia. Regardless of etiology, corneal allodynia is associated with decreased corneal epithelial cell densities, increased epithelial cell size, and decreased numbers and lengths of subbasal nerves despite an unremarkable slit-lamp examination. Therefore, IVCM may be useful in the management of patients with corneal allodynia.

In Vivo confocal microscopic changes of the corneal epithelium and stroma in patients with herpes zoster ophthalmicus.

PURPOSE: To analyze the density and morphology of corneal epithelial cells and keratocytes by in vivo confocal microscopy (IVCM) in patients with herpes zoster ophthalmicus (HZO) as associated with corneal innervation. DESIGN: Prospective, controlled and masked cross-sectional study. METHODS: setting: Single-center study. PATIENTS: Thirty eyes with the diagnosis HZO and their contralateral clinically unaffected eyes, 15 eyes of 15 normal controls. intervention procedures: In vivo confocal microscopy and corneal esthesiometry of the central cornea. MAIN OUTCOME MEASURES: Changes in morphology and density of the superficial and basal epithelial cells and stromal keratocytes, and correlation with corneal sensation. RESULTS: The density of superficial epithelial cells in HZO eyes with severe sensation loss (766.5 ± 25.2 cells/mm(2)) was significantly lower than both healthy control eyes (1450.23 ± 150.83 cells/mm(2)) and contralateral unaffected eyes (1974.13 ± 298.24 cells/mm(2)) (P = .003). Superficial epithelial cell size (1162.5 µm(2)) was significantly larger in HZO eyes with severe loss of sensation, as compared to contralateral (441.46 ± 298.14) or healthy eyes (407.4 ± 47.2µm(2); all P < .05). The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients, controls, and contralateral unaffected eyes. Changes in superficial epithelial cell density and morphology correlated strongly with corneal sensation. CONCLUSIONS: In vivo confocal microscopy reveals profound HZO-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. We demonstrate that these changes strongly correlate with changes in corneal innervation in eyes affected by HZO.

Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial.

IMPORTANCE: The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. OBJECTIVE: To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. DESIGN AND SETTING: Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. PARTICIPANTS: Seventy-five patients with refractory DED. INTERVENTIONS: Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks. MAIN OUTCOMES AND MEASURES: Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. RESULTS: Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P < .001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms. CONCLUSIONS AND RELEVANCE: Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681109.

Topical ranibizumab as a treatment of corneal neovascularization.

PURPOSE: To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). METHODS: This was a prospective, open-label, monocentric, uncontrolled noncomparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up period of 16 weeks. The main corneal NV outcome measures were: neovascular area, the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA. RESULTS: Statistically significant decreases in neovascular area (55.3%, P < 0.001), which lasted through 16 weeks, and VC (59%, P < 0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P = 0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. CONCLUSIONS: Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA.

Unilateral herpes zoster ophthalmicus results in bilateral corneal nerve alteration: an in vivo confocal microscopy study.

PURPOSE: Herpes zoster ophthalmicus (HZO), thought to be a unilateral disease, results in loss of corneal sensation, leading to neurotrophic keratopathy. This study aimed to analyze bilateral corneal nerve changes in patients with HZO by in vivo confocal microscopy (IVCM) and their correlation with corneal sensation as a measure of nerve function. DESIGN: Prospective, cross-sectional, controlled, single-center study. PARTICIPANTS: Twenty-seven eyes with the diagnosis of HZO and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15). METHODS: In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5-5.5 cm), and severe (<2.5 cm) loss of sensation. MAIN OUTCOME MEASURES: Changes in corneal nerve density, total nerve number, main nerve trunks, branching, and tortuosity were evaluated after IVCM and were correlated to corneal sensation, disease duration, and number of recurrences. RESULTS: Eyes with herpes zoster ophthalmicus had a significant (P<0.001) decrease in total nerve length (595.8±358.1 vs. 2258.4±989.0 µm/frame), total number of nerves (5.4±2.8 vs. 13.1±3.8), number of main nerve trunks (2.3±1.1 vs. 4.7±1.2), and number of nerve branches (3.2±2.3 vs. 8.4±3.7) as compared with controls. In the contralateral clinically unaffected eyes, total nerve length (1053.1±441.4 µm/frame), total number of nerves (8.3±2.9), and main nerve trunks (3.1±1.0) also were decreased significantly as compared with controls (P<0.01). Reduced nerve density, total nerve count, main trunks, and tortuosity was correlated significantly with corneal sensation across all subgroups (P<0.001). CONCLUSIONS: Patients with unilateral HZO demonstrated a profound and significant bilateral loss of the corneal nerve plexus as compared with controls, demonstrating bilateral changes in a clinically unilateral disease. Loss of corneal sensation strongly correlated with subbasal nerve plexus alterations as shown by IVCM. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.