Sangita P. Patel

Late‐onset Fuchs endothelial corneal dystrophy (FECD) is characterized by distinct extracellular matrix deposits (guttae) within the basement membrane (Descemet's membrane) of the corneal endothelium. In a recent study published in The Journal of Pathology , Vaitinadapoulé et al (2026) describe the diversity of guttae patterns in FECD through analysis of 500 Descemet's membrane specimens removed during surgery, with genotyping performed in one‐fifth of patients for the commonly associated TCF4 trinucleotide repeat expansion. The diversity and clustering of guttae phenotypes in the total cohort and in those with and without TCF4 association have implications for commonly used diagnostic grading criteria for FECD, the development of therapeutics, and our understanding of disease development. Investigating and embracing this diversity holds promise for advancing our understanding of FECD. © 2026 The Pathological Society of Great Britain and Ireland.

Aims: To determine the associations between measures of oestrogen exposure and Fuchs endothelial corneal dystrophy (FECD) severity. Methods: Clinic-based cross-sectional study of 32 postmenopausal women and 11 men with mild or severe FECD, age>55 years. Participants completed questionnaires for data on demographics, anthropometric factors, medical history and potential risk factors for FECD. Women completed an additional reproductive history questionnaire used to calculate the months of lifetime oestrogen exposure. Slit-lamp biomicroscopy, specular microscopy, corneal Scheimpflug tomography and laboratory testing ( TCF4 repeat expansion quantification, total estradiol, free estradiol, sex hormone binding globulin (SHBG), calcaneal bone density) were performed. Logistic regression models were developed to predict FECD severity based on three-way interactions of each oestrogen exposure measure, sex and TCF4 genotype. Results: 43 patients were enrolled in the study (mild FECD: 17 women, 3 men; severe FECD: 15 women, 8 men). Serum-free estradiol was higher in the severe compared with mild FECD group (0.21±0.2 vs 0.09±0.1 pg/mL; p=0.046). When stratified by sex, men showed no significant associations between oestrogen measures and FECD severity. However, in women, the odds of severe FECD were increased with more months of lifetime oestrogen exposure (all women; log OR (95% credible interval): 1.3 (0.14 to 4.3)), higher concentrations of free estradiol (all women; 2.1 (0.0049 to 10)), greater % free estradiol (only women without TCF4 repeat expansion; 1.3 (0.16 to 3.8)) and higher concentrations of SHBG (only women with TCF4 repeat expansion; 2.2 (0.45 to 9.1)). Conclusions: While the application of these data is constrained by the limited number of participants, a clinic-based sample, small number of men compared with women and single-point measures of serum hormone measures, these data suggest that FECD severity is associated with higher oestrogen exposures in women but not men and may be dependent on TCF4 repeat expansion status.

In Fuchs endothelial corneal dystrophy (FECD), mitochondrial and oxidative stresses in corneal endothelial cells (HCEnCs) contribute to cell demise and disease progression. FECD is more common in women than men, but the basis for this observation is poorly understood. To understand the sex disparity in FECD prevalence, we studied the effects of the sex hormone 17-β estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of HCEnCs grown under physiologic ([O₂]_2.5) and hyperoxic ([O₂]_A) conditions. We hypothesized that E2 would counter the damage of oxidative stress generated at [O₂]_A. HCEnCs were treated with or without E2 (10 nM) for 7–10 days under both conditions. Treatment with E2 did not significantly alter HCEnC density, viability, ROS levels, oxidative DNA damage, oxygen consumption rates, or extracellular acidification rates in either condition. E2 disrupted mitochondrial morphology in HCEnCs solely from female donors in the [O₂]_A condition. ATP levels were significantly higher at [O₂]_2.5 than at [O₂]_A in HCEnCs from female donors only, but were not affected by E2. Our findings demonstrate the resilience of HCEnCs against hyperoxic stress. The effects of hyperoxia and E2 on HCEnCs from female donors suggest cell sex-specific mechanisms of toxicity and hormonal influences.

Purpose To compare the efficacy of phakic intra-ocular lenses in isolation or in combination with corneal crosslinking (CXL) and/or intra-stromal corneal ring segments (ICRS) in keratoconus. Methods Data extracted from the publications meeting the selection. The outcome parameters included mean pre- and post-operative uncorrected distance visual acuity, corrected distance visual acuity (CDVA), sphere and cylinder of refraction and complications. Available data analyzed with Cochrane Review Manager. Results A total of 23 studies including 464 eyes were included. All the parameters showed significant improvement in all subgroups other than CDVA in ACPIOL + CXL subgroup and cylinder in PIOL + CXL subgroups. There was not a significant difference between PCPIOL and ACPIOL in the outcomes, exception was more improvement of CDVA in “ACPIOL only” than” PCPIOL only” subgroup. Conclusion Both PCPIOLs and ACPIOLs are comparably safe and efficient options in management of KCN and their efficacy significantly improves when combined with CXL/ICRS.

Fuchs endothelial corneal dystrophy (FECD) results from genetic and environmental factors triggering mitochondrial and oxidative stress in corneal endothelial cells (CEnCs) leading to CEnC death and corneal opacification. FECD is more common in women than men, but the basis for this observation is unknown. Because FECD is commonly diagnosed around the time of the menopausal transition in women when estrogen levels decrease precipitously, we studied the effects of the potent estrogen,17-β estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of human CEnCs (HCEnCs) under conditions of physiologic 2.5% O ₂ ([O ₂ ] _2.5 ) and under hyperoxic stress ([O ₂ ] _A : room air + 5% CO ₂ ). We hypothesized that E2 would counter the stresses of the hyperoxic environment in HCEnCs. HCEnCs were treated ± 10 nM E2 for 7-10 days at [O ₂ ] _2.5 and [O ₂ ] _A followed by measurements of cell density, viability, reactive oxygen species (ROS), mitochondrial morphology, oxidative DNA damage, ATP levels, mitochondrial respiration (O ₂ consumption rate [OCR]), and glycolysis (extracellular acidification rate [ECAR]). There were no significant changes in HCEnC density, viability, ROS levels, oxidative DNA damage, OCR, and ECAR in response to E2 under either O ₂ condition. We found that E2 disrupted mitochondrial morphology in HCEnCs from female donors but not male donors at the [O ₂ ] _A condition. ATP levels were significantly higher at [O ₂ ] _2.5 compared to [O ₂ ] _A in HCEnCs from female donors only, but were not affected by E2. Our findings demonstrate the overall resilience of primary HCEnCs against hyperoxic stress. The selective detrimental effects of hyperoxia and estradiol on HCEnCs from female but not male donors suggests mechanisms of toxicity based upon cell-sex in addition to hormonal environment.

Background. Recurrence of herpetic keratitis following vaccination has been documented following vaccination with the Zostavax, trivalent flu, hepatitis A, and rabies vaccines. The USFDA and WHO have acknowledged that the novel COVID-19 vaccines similarly have a risk of reactive immunologic-based inflammation, namely, myositis, pericarditis, and Guillain-Barr syndrome. Case Presentation. We present two patients with latent herpetic keratitis who experienced reactivation of keratitis within weeks of COVID-19 vaccination despite prolonged periods of prior latency. A 52-year-old healthy male with no herpes simplex virus (HSV) keratitis recurrences in two years developed visual decline and patchy stromal haze within 24-48 hours of receiving the second Pfizer-BioNTech (COVID-19 BNT162b2) vaccine. A 67-year-old female with chronic neurotrophic keratitis developed her most severe exacerbation of herpes zoster keratitis in over 10 years occurring 2-3 weeks after her first Moderna (mRNA-1273) vaccine, which was later complicated by bacterial superinfection. Conclusions. The COVID-19 vaccines work by generating both adaptive humoral and cellular immune responses in humans, including elevation of anti-spike neutralizing antibody titers, antigen-specific CD4+ and CD8+ T-cell responses, and increased levels of proinflammatory cytokines such as interferon gamma (IFNγ). The general activation of the T-cell-mediated immune response and proinflammatory cytokines such as IFNγ may underlie the role of the COVID vaccines in reactivation of herpetic stromal keratitis and the clinical findings in our reported cases.