Cornea

BACKGROUND/OBJECTIVE: To test the feasibility of a dry eye disease (DED) symptom stratification algorithm previously established for the general population among patients visiting ophthalmologists. SUBJECT/METHODS: This retrospective cross-sectional study was conducted between December 2015 and October 2021 at a university hospital in Japan; participants who underwent a comprehensive DED examination and completed the Japanese version of the Ocular Surface Disease Index (J-OSDI) were included. Patients diagnosed with DED were stratified into seven clusters using a previously established symptom-based stratification algorithm for DED. Characteristics of the patients in stratified clusters were compared. RESULTS: In total, 426 participants were included (median age [interquartile range]; 63 [48-72] years; 357 (83.8%) women). Among them, 291 (68.3%) participants were diagnosed with DED and successfully stratified into seven clusters. The J-OSDI total score was highest in cluster 1 (61.4 [52.2-75.0]), followed by cluster 5 (44.1 [38.8-47.9]). The tear film breakup time was the shortest in cluster 1 (1.5 [1.1-2.1]), followed by cluster 3 (1.6 [1.0-2.5]). The J-OSDI total scores from the stratified clusters in this study and those from the clusters identified in the previous study showed a significant correlation (r = 0.991, P < 0.001). CONCLUSIONS: The patients with DED who visited ophthalmologists were successfully stratified by the previously established algorithm for the general population, uncovering patterns for their seemingly heterogeneous and variable clinical characteristics of DED. The results have important implications for promoting treatment interventions tailored to individual patients and implementing smartphone-based clinical data collection in the future.

BACKGROUND: Sjögren's syndrome (SjS) is a rare autoimmune disease, and despite our knowledge of SjS, we still lack effective treatments. Chloroquine drugs used to treat autoimmune diseases are still the primary medicine for SjS but increase the risk of chloroquine retinopathy. OBJECTIVES: The objective of this study is to use Optical Coherence Tomography Angiography (OCTA) images to monitor the microvascular changes in the fundus of SjS patients after hydroxychloroquine (HCQ) treatment and the feasibility of using them as diagnostic indicators. DESIGN: This is a retrospective observational cohort study. METHODS: Twelve healthy controls (HCs group; 24 eyes), 12 SjS patients (SjS group; 24 eyes), and 12 SjS patients treated with HCQ (HCQ group; 24 eyes) were recruited. Three-dimensional OCTA images of the retina were collected, and microvascular density was calculated for each eye. OCTA image segmentation for analysis was conducted using the central wheel division method (C1-C6), hemisphere segmentation method (SR, SL, IL, and IR), and the early treatment of diabetic retinopathy study method (ETDRS) (R, S, L, and I). RESULTS: Retinal microvascular density was significantly lower in the SjS patients compared to the HCs group (p < 0.05) and much lower in the HCQ group compared to the SjS patients (p < 0.05). The SjS and HCQ groups differed in the I, R, SR, IL, and IR regions in the superficial and deep retina and the S region in the superficial retina. The ROC curves of the relationship between the HCs and SjS groups and between the SjS and HCQ groups demonstrated good classification accuracy. CONCLUSION: HCQ may contribute significantly to the microvascular alteration in SjS. Microvascular alteration is a potential marker with adjunctive diagnostic value. The MIR and the OCTA images of I, IR, and C1 regions showed high accuracy in minoring the alteration.

BACKGROUND: Meibomian gland dysfunction (MGD) reduces quality-of-life and hinders work productivity of millions of patients, with high direct and indirect societal costs. Thickened meibum obstructs the glands and disrupts ocular surface health. Heating the eyelids to soften and express meibum from the glands can be beneficial. The most accessible method for eyelid warming uses heated, wet towels. However, the efficacy of this treatment is reliant on the methodology, and evidence-based best-practice recommendations are needed. PURPOSE: To evaluate the literature on hot towels in MGD treatment and recommend a best-practice protocol for future research and patient treatment. METHODS: Studies were identified through PubMed on the May 28, 2021, with the search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR "dry eye" OR DED). All relevant original articles with English full-text were included. RESULTS: The search yielded 903 results, of which 22 met the inclusion criteria. Across studies, hot towels were found to be effective at reducing ocular symptoms. However, without reheating, the temperature quickly fell below the therapeutic range, which was deemed to be between 40 °C and 47 °C. Towels heated to around 45 °C and reheated every-two minutes were most effective at increasing eyelid temperature, comparable or better than several commercially available eyelid warming devices. No adverse effects were reported in the studies. CONCLUSION: Hot towel treatment effectively warms the eyelids and reduces ocular symptoms, but must be standardized, and towels reheated to achieve maximum benefit. Future research should assess patient satisfaction with different hot towel treatment methods that reheat or replace the towel at least every-two minutes, to establish which methods yield the greatest compliance. Guidelines or clinical recommendations that do not mention the need for regular reheating during hot towel compress treatment should be updated to include this.

BACKGROUND/AIMS: To establish normative curves for axial length and corneal curvature in the first decade of life. METHODS: This is a cross-sectional study from a single institution in the United States. Children from 0- to 10-years of age with no underlying ocular pathology were prospectively enrolled to obtain ultrasound biometry and hand-held keratometry while under anaesthesia for an unrelated procedure. Older cooperative children had optical biometry obtained in-office. Logarithmic quantile regression models were used to determine the change in axial length and average keratometry as a function of age. RESULTS: Single-eye measurements from 100 children were included. 75% of children were White and 49% female. Median axial length ranged from 20.6 mm (IQR, 20.2 to 21.1 mm) at age one year to 23.1 mm (IQR, 22.5 to 23.8 mm) at age ten years. Median average keratometry ranged from 44.1 D (IQR, 42.6 to 45.4 D) at age one year to 43.5 (IQR, 42.2 to 44.0 D) at age ten years. As age increased, there was a significant increase in axial length (0.74 mm per doubling of age; 95% CI, 0.62 to 0.82 mm), and a non-significant trend towards lower average keratometry (-0.21 D per doubling of age; 95% CI, -0.62 to 0.08 D). CONCLUSIONS: We provide a set of normative charts for axial length and corneal curvature which may facilitate the identification of eyes outside the normal range and assist in the management of ocular conditions such as glaucoma or cataract.

PURPOSE: To describe the clinical features and visual outcomes of eyes with conjunctival haptic erosion after sutureless intrascleral (SIS) fixated intraocular lens (IOL) placement. DESIGN: Retrospective case series. SUBJECTS: Patients experiencing haptic erosion after SIS fixation between January 1, 2013, and March 1, 2022. METHODS: A multicenter, multisurgeon, retrospective review. MAIN OUTCOME MEASURES: Clinical features, visual outcomes, and treatment options following haptic erosions after SIS fixation. RESULTS: Nineteen eyes with haptic erosion were identified. The mean age at initial SIS fixation was 64 ± 12 years (range, 38-81 years). There were 5 (26%) eyes with a history of conjunctiva involving ocular surgery, including scleral buckle surgery and tube shunt surgery. Trocar-assisted fixation was performed in 15 (79%) eyes, whereas needle fixation was used in 4 (21%) eyes. Eighteen (95%) sets of haptics were flanged with a low temperature cautery. Seventeen (90%) sets of haptics were externalized superiorly and inferiorly, and 2 (10%) sets of haptics were externalized nasally and temporally. Haptics were covered by conjunctiva in 14 (74%) eyes and by scleral flap in 5 (26%) eyes. All patients experienced a single haptic erosion, of which 8 (43%) were located superiorly, 9 (47%) inferiorly, and 2 (10%) temporally. The mean interval between the initial SIS fixation and haptic erosion was 278 ± 437 days. After correction of the erosion, 18 (95%) eyes had a stable IOL at the last follow-up, with no recurrence of haptic erosion. In this series, there were no cases of endophthalmitis. CONCLUSIONS: Haptic erosion is a notable complication after SIS fixated IOL surgery but may be repaired with favorable visual outcomes. Careful evaluation of the conjunctiva should be considered before the surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Purpose: Pupil center is an important anchor point in corneal refractive surgery, which may affect by body position. This study investigated the feasibility of using a smartphone application in measurement of posture-related pupil center shifts. Methods: Images of undilated eyes were captured for 25 participants (age: 18-38 years) at a distance of 40 cm in four body positions (seated, supine, right lateral, and left lateral) under controlled lighting conditions. During taking images, a smartphone application was used to guide positioning without head rotation and tilt. From the images, the location of the pupil center and pupil diameter with respect to the limbus boundary were measured. Results: According to the data obtained by the smartphone application, pupil center was located slightly nasal and superior to the limbus center in the seated position, and it shifted more nasally and superiorly (p < 0.001, OD 0.54 ± 0.11 mm, OS 0.57 ± 0.14 mm) in the supine position. When body position switched between left and right lateral positions, the pupil centers of both eyes shifted along the direction of gravity (p < 0.05), and no significant shift occurred along the longitudinal axis. Moreover, pupil constriction was observed when the body position changed from seated to supine position (p < 0.001, OD 0.64 ± 0.57 mm, OS 0.63 ± 0.58 mm). Conclusion: Posture-related pupil center shift may be larger than the error tolerance of centration in corneal refractive surgery, which might be difficult to measure by the existing instruments. An accessible application is necessary for evaluating the shift of pupil center and guiding centration during the surgery.

PURPOSE: The aim of this study was to compare outcomes between cases of Acanthamoeba keratitis (AK) diagnosed and treated with or without the use of in vivo confocal microscopy (IVCM). METHODS: We performed a retrospective comparative case series of 26 eyes of 23 patients diagnosed with AK at the Massachusetts Eye and Ear Infirmary over a 5-year period. The characteristics of all identified cases were summarized. We compared the time from presentation to diagnosis of AK (primary outcome), visual acuity, and rates of therapeutic penetrating keratoplasty between eyes diagnosed by culture-only group (n = 8) and by IVCM to diagnose AK (n = 9) and later confirmed by culture (IVCM/C group). RESULTS: The diagnostic delay was significantly longer in the culture only group (25 ± 29 days) compared with the IVCM/C group (3 ± 3 days, P < 0.01). At 6 months, there was a significant difference in best-corrected visual acuity between the culture-only group (1.46 ± 1.07, n = 7) and the IVCM/C group (0.22 ± 0.22, n = 8), after adjusting for initial baseline visual acuity (P = 0.02). Therapeutic penetrating keratoplasty was performed in 50% of culture-only (n = 7) and 11% of IVCM/C group eyes (n = 9), but this was not statistically significant (P = 0.13). CONCLUSIONS: IVCM can expedite the diagnosis of AK, and its use as an adjunct tool in the diagnosis of AK may result in better patient outcomes compared with basing treatment decisions on corneal cultures alone.

BACKGROUND: Ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) is a recently developed surgical procedure that has shown promising results for the management of various corneal endothelial diseases. OBJECTIVES: To evaluate the outcomes of the UT-DSAEK to the Descemet membrane endothelial keratoplasty (DMEK). DESIGN: A systematic analysis of the studies comparing UT-DSAEK with DMEK by evaluating one or more outcomes (vision, complications, and post-operative endothelial cell counts) was performed. The meta-analysis was done if two or more studies reported a common outcome. METHODS: We used PubMed, EMBASE, and SCOPUS databases to identify articles comparing the outcomes of UT-DSAEK with DMEK and performed a meta-analysis using RevMan, version 5.4. RESULTS: A total of six studies were included in this review (two randomized clinical trials and four non-randomized comparative studies). Our analysis showed the patients who underwent DMEK cases showed better visual outcomes with a mean difference of 0.06 LogMAR (95% CI: 0.04-0.09) in BCVA, albeit with i 2 of 52% (heterogenous values). The evidence was weak, with the most weightage on retrospective studies. UT-DSAEK showed significantly fewer complications such as graft dislocations, with an odds ratio of 0.25 (95% CI: 0.13-0.48). There was no significant difference in the endothelial cell counts with a mean difference of 86.34 (95%CI: -133.09 to -305.77). CONCLUSION: Although the literature is limited on UT-DSAEK with post-operative visual acuity that could be practically at par with DMEK, lesser complication rates and comparable post-operative endothelial cells could be a suitable alternative to DMEK for corneal endothelial pathologies.

Despite extensive study, the mechanisms underlying pain after axonal injury remain incompletely understood. Pain after corneal refractive surgery provides a model, in humans, of the effect of injury to trigeminal afferent nerves. Axons of trigeminal ganglion neurons that innervate the cornea are transected by laser-assisted in situ keratomileusis (LASIK). Although most patients do not experience postoperative pain, a small subgroup develop persistent ocular pain. We previously carried out genomic analysis and determined that some patients with persistent pain after axotomy of corneal axons during refractive surgery carry mutations in genes that encode the electrogenisome of trigeminal ganglion neurons, the ensemble of ion channels and receptors that regulate excitability within these cells, including SCN9A, which encodes sodium channel Nav1.7, a threshold channel abundantly expressed in sensory neurons that has been implicated in a number of pain-related disorders. Here, we describe the biophysical and electrophysiological profiling of the P610T Nav1.7 mutation found in two male siblings with persistent ocular pain after refractive surgery. Our results indicate that this mutation impairs the slow inactivation of Nav1.7. As expected from this proexcitatory change in channel function, we also demonstrate that this mutation produces increased spontaneous activity in trigeminal ganglion neurons. These findings suggest that this gain-of-function mutation in Nav1.7 may contribute to pain after injury to the axons of trigeminal ganglion neurons.NEW & NOTEWORTHY Mechanisms underlying pain after axonal injury remain elusive. A small subgroup of patients experience pain after corneal refractive surgery, providing a human pain model after well-defined injury to axons. Here we analyze a mutation (P610T) in Nav1.7, a threshold sodium channel expressed in nociceptors, found in two siblings with persistent ocular pain after refractive surgery. We show that it impairs channel slow inactivation, thereby triggering inappropriate repetitive activity in trigeminal ganglion axons that signal eye pain.

PURPOSE: The purpose of this study was to establish a murine model of endothelial keratoplasty. METHODS: Endothelial keratoplasty (EK) was performed using C57BL/6 donor and BALB/c recipient mice. The central endothelium and Descemet membrane were removed from the recipient cornea, and a 1.5-mm posterior lamellar donor graft was made adherent to the recipient cornea with a small amount of viscoelastic. Mice were followed through slitlamp microscopy postoperatively, and OCT was used to assess the cornea and anterior chamber and measure central corneal thickness. Histology and immunohistochemistry were performed to confirm graft adherence and endothelial cell morphology. RESULTS: Successfully attached EK grafts were visualized in all transplanted animals. Histology and immunostaining confirmed proper graft orientation and adherence, as well as the presence of donor endothelium on transplanted grafts. We observed maximal corneal edema in all animals at day 1 postoperatively which gradually subsided. EK graft survival was 97% at 8 weeks. CONCLUSIONS: In this study, we describe a novel murine model for EK which we anticipate will enable detailed investigation into the cellular and molecular mechanisms involved in EK pathobiology.

The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy. We and others have previously shown that mast cells mediate tissue inflammation by recruiting other immune cells. However, despite their well-known characteristics of secreting various inflammatory mediators, whether mast cells contribute to the immune cell aggregation and activation, and acinar dystrophy of the aged lacrimal gland has not been investigated. Here, we demonstrate the role of mast cells in age-related lacrimal gland pathophysiology using mast cell-deficient (cKitw-sh) mice. Our data demonstrated a significant increase in mast cell frequencies and immune cell infiltration in the lacrimal gland of aged mice. Interestingly, mast cell deficiency resulted in a substantial reduction in inflammation and preservation of lacrimal gland structure, suggesting that mast cells mediate the aging process of the lacrimal gland.

Vaccines against coronavirus disease 2019 (COVID-19) have played an important global role in reducing morbidity and mortality from COVID-19 infection. While the benefits of vaccination greatly outweigh the risks, adverse events do occur. Non-ocular adverse effects of the vaccines have been well-documented, but descriptions of ophthalmic effects remain limited. This systematic review aims to provide an overview of reported cases of corneal adverse events after receiving vaccination against COVID-19 and to compile existing clinical data to bring attention to these phenomena. Our review discusses corneal graft rejection, including proposed mechanisms, herpetic keratitis, and other reported corneal complications. Ophthalmologists and primary care physicians should be aware of such possible associations.

PURPOSE: To assess the effect of corneal scarring location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer. METHODS: Prospective, longitudinal, case-control study. Bilateral corneal nerve density and corneal sensation was analyzed centrally and peripherally in 24 healthy controls and 23 patients with unilateral HSV-related corneal scars using IVCM. RESULTS: In the central scar (CS) group, total nerve density in the central cornea remained significantly lower compared to controls at follow-up (11.05 ± 1.97mm/mm2, p < 0.001), and no significant nerve regeneration was observed (p = 0.090). At follow-up, total nerve density was not significantly different from controls in the central and peripheral cornea of peripheral scar (PS) group (all p > 0.05), and significant nerve regeneration was observed in central corneas (16.39 ± 2.39mm/mm2, p = 0.007) compared to baseline. In contralateral eyes, no significant corneal nerve regeneration was observed in central or peripheral cornea of patients with central scars or peripheral scars at 1-year follow-up, compared to baseline (p > 0.05). There was a positive correlation between corneal nerve density and sensation in both central (R = 0.53, p < 0.0001) and peripheral corneas (R = 0.27, p = 0.0004). In the CS group, the corneal sensitivity was <4 cm in 4 (30.8%) and 7 (53.8%) patients in the central and peripheral corneas at baseline, and in 5 (38.5%) and 2 subjects (15.4%) at follow-up, whereas in the PS group only 1 patient (10%) showed a corneal sensation < 4cm in the central cornea at baseline, and only 1 (10.0%), 3 (30.0%) and 1 (10.0%) patients at follow-up in the central, affected and opposite area of the cornea, respectively. CONCLUSION: The location of HSV scarring in the cornea affects the level of corneal nerve regeneration. Eyes with central corneal scar have a diminished capacity to regenerate nerves in central cornea, they show a more severe reduction in corneal sensation in the central and peripheral cornea that persist at follow-up, and they have a reduced capability to restore the corneal sensitivity above the cut-off of 4 cm. Thus, clinicians should be aware that CS patients would benefit from closer monitoring for potential complications associated with neurotrophic keratopathy, as they have a lower likelihood for nerve regeneration.

PURPOSE: The aim of this study was to evaluate the cases of herpes simplex and zoster ophthalmicus after SARS-CoV-2 vaccination and assess the clinical presentations in patients. METHODS: A retrospective analysis of cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS) between December 11, 2020, and July 1, 2022. Patients diagnosed with herpes simplex ophthalmicus (HSO) and herpes zoster ophthalmicus (HZO) after vaccination with BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen) were included in the study. We performed a descriptive analysis of patient demographics, history, and ophthalmic and systemic clinical presentations. The correlations between vaccine type and continuous variables were assessed by the one-way analysis of variance test. In addition, we used the Pearson χ 2 test to assess the association between 3 vaccines and categorical variables. A post hoc analysis was performed between HSO and HZO onset intervals after vaccination, dose, and vaccine type. The 30-day risk analysis was also performed for HSO and HZO onset postvaccination using the reverse Kaplan-Meier analysis. RESULTS: A total of 1180 cases of HZO (983, 83.30%) and HSO (180, 15.25%) were reported. The mean age of patients with HZO and HSO was 59.02 ± 19.05 and 52.68 ± 17.83 years, respectively. Most of the cases of HZO (795, 80.87%) and HSO (131, 72.78%) were reported in patients who received BNT162b2. In the cohort, 63.28% and 65.56% diagnosed with HZO and HSO were women. About one third of HZO (36.52%) and HSO (35.56%) cases were reported after the first dose. More than half of the cases of HZO (61.34%) and HSO (64.45%) were reported within the first 2 weeks after vaccination. The estimated crude reporting rate (per million doses) in the United States was 0.25, 0.22, and 0.47 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The onset interval for HZO was significantly shorter in patients who received BNT162b2 (20.51 ± 56.20 days, P = 0.030) compared with patients who received mRNA-1273 (36.56 ± 108.67 days) and Ad26.COV2.S (39.66 ± 60.15 days) vaccines. The 30-day risk analysis showed a significantly higher risk of HZO after BNT162b2 than the other 2 vaccines ( P = 0.011). CONCLUSIONS: The low crude reporting rate suggests that HZO and HSO after SARS-CoV-2 vaccination occur rarely. This study provides insights into the possible temporal association between reported HSO and HZO after SARS-CoV-2 vaccines; however, further investigations are required to delineate the possible underlying immunological mechanisms.