Evaluating the efficacy and safety of therapeutic interventions for corneal neuropathy: A systematic review.

Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n=6 studies), dietary supplements (n=4), anti-glycemic agents (n=3), combination therapy (n=3), supportive therapies (n=2) and systemic pain pharmacotherapies (n=2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve capacity to synthesize data to inform evidence-based based care. Protocol registration: PROSPERO ID: CRD42022348475.

Quantifying corneal immune cells from human in vivo confocal microscopy images: Can manual quantification be improved with observer training?

Manually quantifying immune cells (ICs), commonly considered dendritic cells, in the corneal epithelium from in vivo confocal microscopy (IVCM) images can be influenced by observer bias. This study sought to evaluate the repeatability of manual IC quantification. Cell counts were first performed for 184 non-overlapping IVCM images by a single observer. Quantifications were undertaken to establish the total cell numbers per image, and the numbers of three cell morphological subtypes: mature ICs (with elongated dendrites), immature ICs (with short- or non-discernible dendrites) and globular cells (with large bodies and no visible dendrites). Cell counts were then repeated by the same observer, and independently undertaken by a second observer. Prior to these counts, both observers undertook an agreement 'training' process to define IC appearance and delineate the morphological subtypes. Total IC counts demonstrated excellent intra- and inter-observer reliability (intraclass correlation coefficients (ICC) > 0.90). Bland-Altman plots showed that interobserver measurement bias increased as a function of the total IC number in the image prior to consensus training. For total IC counts after the observer training process, there was no significant interobserver measurement bias. For IC morphological subtypes, there was a positive relationship between the mean inter-observer difference and average cell count for mature ICs and globular cells, but not immature ICs. In conclusion, higher variability in manual corneal IC counts exists when more cells are present in an IVCM image. Implementing an observer training process reduced inter-observer variability and minimised systematic measurement error.

Identification of presumed corneal neuromas and microneuromas using laser-scanning in vivo confocal microscopy: a systematic review.

BACKGROUND/AIMS: This systematic review critically evaluated peer-reviewed publications describing morphological features consistent with, or using terms related to, a 'neuroma' or 'microneuroma' in the human cornea using laser-scanning in vivo confocal microscopy (IVCM). METHODS: The review was prospectively registered on PROSPERO (CRD42020160038). Comprehensive literature searches were performed in Ovid MEDLINE, Ovid Embase and the Cochrane Library in November 2019. The review included primary research studies and reviews that described laser-scanning IVCM for examining human corneal nerves. Papers had to include at least one of a pre-specified set of keyword stems, broadly related to neuromas and microneuromas, to describe a corneal nerve feature. RESULTS: Twenty-five papers (20 original studies; 5 reviews) were eligible. Three original studies evaluated corneal nerve features in healthy eyes. Most papers assessed corneal nerves in ocular and systemic conditions; seven studies did not include a control/comparator group. There was overlap in terminology used to describe nerve features in healthy and diseased corneas (eg, bulb-like/bulbous, penetration, end/s/ing). Inspection of IVCM images within the papers revealed that features termed 'neuromas' and 'microneuromas' could potentially be physiological corneal stromal-epithelial nerve penetration sites. We identified inconsistent definitions for terms, and limitations in IVCM image acquisition, sampling and/or reporting that may introduce bias and lead to inaccurate representation of physiological nerve characteristics as pathological. CONCLUSION: These findings identify a need for consistent nomenclature and definitions, and rigorous IVCM scanning and analysis protocols to clarify the prevalence of physiological, as opposed to pathological, corneal nerve features.

Does Occupation Influence Selection of Contact Lens Material?

OBJECTIVE: Long-term follow-up of contact lens (CL) wearers leads to better understanding of the factors leading to changes in CL trends. This study is an attempt to ascertain these factors in an emerging market like India. Factors like occupation were analyzed to determine if these contributed to changes in selection of CL materials in this article. METHODS: Occupations were categorized as per the norms of International Standard Classification of Occupations-2008 (International Labor Organization, United Nations organization). RESULTS: A majority of lens wearers were professionals and hydrogel lens materials were the lenses of choice among most of the lens wearers. There was a significant variation in CL material with different occupations (χ=19.29, P=0.037). CONCLUSION: To conclude, employment and affordability influenced the selection of lens materials.

Contact lens trends over three decades in a hospital-based practice in India.

BACKGROUND: Contact lens fittings in a hospital-based practice are different from those in private practices because of specialised conditions. Few studies have been published on material preferences of such wearers, especially in long-term wearers. The aim of this study is to document contact lens prescribing trends in a hospital-based practice among long-term lens wearers and to identify their demographic profile. METHODS: Subjects reporting to a contact lens clinic of a tertiary eye-care centre in India from 1 January 2014 to 31 December 2014, with a minimum of five years of lens wear, were included in the study. Data were collected retrospectively from the electronic medical charts of these subjects. RESULTS: Three hundred and sixty subjects were included in the study. The average duration of contact lens wear among the subjects was 9 ± 5 years (range: 5-35 years). The average age of the subjects was 31.38 ± 11.75 years (age range: 5-78 years). Hydrogel material and soft spherical type were preferred by most of the soft lens wearers (53 per cent). Eighty per cent of subjects followed hand hygiene and cleaning regimen practices. CONCLUSION: The preference for monthly replacement lenses and silicone hydrogel material increased over the years. Regular after-care consultations could enforce the need for compliance with hand hygiene and cleaning regimens among lens wearers.

Unique hard scleral lens post-LASIK ectasia fitting.

PURPOSE: This case report describes an experience with prosthetic replacement of ocular surface ecosystem (PROSE) device in an Indian patient with post-LASIK corneal ectasia. CASE REPORT: Keratoconus and corneal ectasia (post-LASIK) are characterized by progressive thinning and steepening of the cornea. Common symptoms experienced by patients in such conditions range from mild to severe vision impairments to an array of visual symptoms such as glare and ghosting. Scleral lenses are considered a vision-saving device when all other modalities fail. The patient in this case report had larger palpebral aperture, steeper cornea, and increased toricity of the sclera. Although a larger-diameter device is preferable in steeper corneas, a device with a smaller diameter and a flatter haptic was prescribed because of scleral toricity. There is a need to study scleral profile as well because scleral toricity can produce symptoms in patients even after 6 hours of device wear. After a few days of adaptation, the vault of the PROSE device can change because of haptic alignment on the sclera. CONCLUSIONS: This case report gives an overview of how the scleral profile can have an effect on the corneal/contact lens relationship when using a PROSE device.

An ocular surface prosthesis for keratoglobus and Terrien's marginal degeneration.

PURPOSE: This case report describes the challenges in fitting corneas using the prosthetic replacement of ocular surface ecosystem (PROSE) device in a unique case of bilateral keratoglobus (KG) with Terrien's marginal degeneration (TMD). CASE REPORT: KG and TMD are uncommon corneal ectatic conditions, characterized by protrusion and thinning of the cornea. Optical correction with spectacles is limited, as this may not provide the best-corrected visual acuity because of irregular corneal astigmatism. Corneal gas-permeable lenses can provide optimal vision, but they have poor fitting characteristics in advanced stages. The PROSE device has the advantage of masking the irregularity of the cornea with a tear lens and a contact lens power that provides a smooth refractive surface. This case report describes the fitting aspects of the PROSE device in a case diagnosed with KG and TMD. A generous vault allows the PROSE device to sink into the conjunctiva more, causing impingement, but a PROSE with higher vault is required as corneal clearance decreases with wear time. Corneal thickness measurements during the trial can give a better idea of corneal edema expected after prescribing the PROSE device. Optical coherence tomography is a useful tool for measuring diurnal changes in the corneal thickness and vault over a period in such challenging cases. CONCLUSIONS: Modification of not only the vault but also the haptic and total diameter of the device is required to achieve an optimal fit. Though challenging, successful fitting of the scleral lens in ectatic corneas is attainable, with the aid of anterior imaging and spline technologies.

PROSE for irregular corneas at a tertiary eye care center.

OBJECTIVE: The aim of this study was to report and discuss the clinical experience with PROSE (Prosthetic Replacement of Ocular Surface Ecosystem) practice at a tertiary eye care hospital. METHODS: Retrospective data of patients who were prescribed PROSE during April 2011 to March 2012 in a tertiary eye care center in south India were analyzed. Data collected include patient demographics, indications of scleral lens fitting, previous correction modality, PROSE parameters, best-corrected visual acuity (BCVA) with spectacles, and BCVA with PROSE at initial assessment and few hours of wear. The BCVA before (with glasses) and after PROSE fitting was recorded in logMAR units. RESULTS: The age of the patients ranged between 13 and 68 years (male:female 60:25) with a mean age of 32.44±13.45 years. Mean BCVA improved by 0.3 logMAR units (3 lines) after fitting with PROSE. There was a statistically significant difference between pre- and post-PROSE BCVA (P=0.0001). Failure of rigid gas-permeable lens fitting or intolerance was the common indication for PROSE in corneas with irregular astigmatism (refractive conditions). The other reasons for which PROSE was prescribed were pain, photophobia, comfort, ghosting of images, and frequent loss of smaller lenses. Toric scleral haptic was indicated in 62 eyes. The diameter, vault, and haptic measurements of PROSE in ocular surface disorders were much less and flatter than that of refractive conditions. CONCLUSIONS: PROSE device is a very useful alternative for irregular corneas to improve visual acuity, to improve comfort, and for symptomatic relief.

Morphological and functional correlates in Goldmann-Favre syndrome: a case series.

The purpose of this study is to describe the correlation of findings between results from spectral domain optical coherence tomography (SD-OCT) and microperimetry in a case series regarding patients with Goldmann-Favre syndrome. Goldmann-Favre syndrome is a rare autosomal recessive hereditary vitreo-retinal degeneration that impacts the functionality of vision in subjects. Three men with this condition were assessed and subjected to microperimetry and SD-OCT. Two of the men were brothers. This study finds that the retinoschisis and macular cystoid changes noted in the SD-OCT matched the scotomas revealed by the microperimetry. The findings of each of the individual cases are reported herein.

Macular pigment optical density in a South Indian population.

PURPOSE. To estimate the normal value of macular pigment optical density (MPOD) in an adult south Indian sample. METHODS. Three hundred eyes of 161 healthy volunteers (30 men and 30 women in each of the age groups of 20-29, 30-39, 40-49, 50-59, and ≥60 years) underwent MPOD measurement with a macular densitometer. Thirty-two eyes were also checked for intersession variability. RESULTS. The mean MPODs in the Indian sample were 0.64 ± 0.23 log unit at 0.25° eccentricity, 0.50 ± 0.21 log unit at 0.5°, 0.37 ± 0.19 log unit at 1.00°, and 0.21 ± 0.16 log unit at 1.75°. At all the foveal eccentricities, the MPOD showed an increase from 20 to 29 to 30 to 39 years of age and thereby showed a decrease with age. The men aged 40 to 49 years had significantly higher MPOD than did the women (0.75 vs. 0.62 log unit, P = 0.039), and the women aged 50 to 59 years had higher MPOD than did the men (0.71 vs. 0.57 log unit, P = 0.019). There was no significant intersession or interocular variation. CONCLUSIONS. This study establishes the MPOD normogram in an adult Indian sample.