Rohit Shetty

SignificanceEarly detection of keratoconus (KC), a progressive corneal disorder, remains a major clinical challenge. Polarization-sensitive optical coherence tomography (PS-OCT) is an advanced imaging technique that can quantify corneal birefringence, offering insight into collagen organization and microstructural integrity.ApproachA total of 359 eyes were examined and evaluated. This study explores PS-OCT-derived phase retardation (PR) and corneal sublayer thickness as potential diagnostic biomarkers for healthy, subclinical (SKC), and KC eyes. Further, the performance of AI-based classification models developed from PS-OCT, Pentacam, and MS-39 data were compared, using random forest classifier trained with a leave-one-out methodology and identical hyperparameter settings.ResultsAll AI models demonstrated comparable accuracy among devices for healthy and KC detection. However, SKC classification differed from Pentacam and MS-39. Here, 39.5% of the SKC eyes were reclassified as healthy by PS-OCT, compared with 27.5% by Pentacam and 30.3% by MS-39. The average diagnostic performance of PS-OCT included an AUC, precision, recall, F1 score, and accuracy of 0.91, 83%, 82%, 0.82, and 82%, respectively. For the Pentacam, the same were 0.95, 87%, 86%, 0.86, and 86%, respectively. For the MS-39, the same were 0.94, 86%, 86%, 0.85, and 86%, respectively.ConclusionsOverall, AI model agreement was strong for healthy and KC groups but varied in SKC. PS-OCT provides complementary diagnostic value and may refine subclinical KC detection for safer refractive surgery decisions.

Purpose: refractive surgery, such as LASIK and SMILE, induces a wound healing response that leads to significant corneal stromal remodeling. We have shown that the protein profile in the stroma changes dramatically immediately post-surgery. However, the methylation status of the DNA post-refractive surgery remains unknown. Design/Participants: DNA methylation study. Refractive surgery (SMILE/LASIK) performed on donor eye globes. Method: we investigated the epigenetic changes post-surgery in relation to long term ECM remodeling in an experimental ex vivo study design. Donor globes (n = 19) were obtained from the eye bank. Three globes served as non-surgical controls while SMILE (-6DS) and LASIK surgery (-6DS) were performed on eight globes each and incubated for 3 days and 2 weeks (n = 4 per group per time point). Here, we compared the DNA methylation landscapes of LASIK and SMILE stroma using the Illumina Infinium Human Methylation 850 EPIC array (HM850). Results: significant changes in DNA methylation patterns were observed post-operatively in both LASIK and SMILE groups. Specific genes involved in the activation of actin cytoskeleton and inflammation (smad3, prkca and ssh2) showed hypomethylation in LASIK after 2 weeks and LASIK SMILE after 3 days, respectively, suggesting their active role in corneal repair. The genes (gaa, gstm1, mgat1, galnt9 and galnt5) involved in sphingolipid metabolism and mucin biosynthesis showed hypomethylation in SMILE after 3 days. Conclusions: our results suggest that altered DNA methylation patterns may have relevance to the development of complications of haze post-refractive surgery. It also presents the opportunity to utilize drugs that regulate chromatin remodeling for optimal outcomes.

Optical coherence tomography (OCT) has gained momentum on segmenting anterior corneal substructures, such as treatment-induced flaps and lenticule cuts created by femtosecond lasers. However, recent semi-automated methods rely on manual markers, which can introduce bias and variability. In this work, we present an automated algorithm designed to overcome the limitations in the geometric quantification of intrastromal cuts produced by two different femtosecond lasers, using a unique imaging system. Our analysis, conducted on peri-operative segmentations of goat eyes, aims to demonstrate the method’s potential for contributing to ongoing efforts and enhancing clinical outcomes in refractive surgery treatment.

Background: This study aims to assess systemic risk factors in diabetes mellitus (DM) patients and predict diabetic retinopathy (DR) using a Random Forest (RF) classification model. Methods: We included DM patients presenting to the retina clinic for first-time DR screening. Data on age, gender, diabetes type, treatment history, DM control status, family history, pregnancy history, and systemic comorbidities were collected. DR and sight-threatening DR (STDR) were diagnosed via a dilated fundus examination. The dataset was split 80:20 into training and testing sets. The RF model was trained to detect DR and STDR separately, and its performance was evaluated using misclassification rates, sensitivity, and specificity. Results: Data from 1416 DM patients were analyzed. The RF model was trained on 1132 (80%) patients. The misclassification rates were 0% for DR and ~20% for STDR in the training set. External testing on 284 (20%) patients showed 100% accuracy, sensitivity, and specificity for DR detection. For STDR, the model achieved 76% (95% CI-70.7%–80.7%) accuracy, 53% (95% CI-39.2%–66.6%) sensitivity, and 80% (95% CI-74.6%–84.7%) specificity. Conclusions: The RF model effectively predicts DR in DM patients using systemic risk factors, potentially reducing unnecessary referrals for DR screening. However, further validation with diverse datasets is necessary to establish its reliability for clinical use.

Background: Immunologic and inflammatory adverse effects following vaccination against COVID-19 are being reported. While some reactions may develop denovo others concern its immunogenic effect in patients with pre-existing inflammatory conditions. Methods: Retrospective consecutive patients diagnosed with ocular inflammatory manifestations within 8 weeks of receiving COVID-19 vaccination who presented to a tertiary eye care centre in South India. Results: Ninety-eight eyes of 67 patients presenting with ocular inflammatory manifestations within 8 weeks following COVID-19 vaccination were studied. The mean age was 43 years (+/- 14.82; range 19–80 years). The most common presentations were anterior uveitis (n = 31, 31.7%), followed by panuveitis (n = 24, 24.5%). The mean time to onset of symptoms was 25 days (+/- 15.48; range 2–55 days) following a dose of vaccine. Among all patients, 39 (58.2%) had a previous history of ocular inflammation. Mean presenting visual acuity was 0.4 (0-4) logMAR units and mean final visual acuity was 0.2 (0-4) logMAR units. The causes for reduced vision included of cystoid macular edema (n=2, 2%), chorioretinal atrophy (n=2.2%), optic atrophy (n=1.1%), retinal vascular occlusion (n=1.1%) and acute retinal necrosis (n=1.1%). Conclusion: Infective and immunogenic adverse events should be watched out for after COVID-19 vaccination. It is difficult to establish causality for such manifestations, nevertheless, most of them were mild and had good final visual outcomes.

One of the most remarkable advancements in medical treatments of corneal diseases in recent decades has been corneal transplantation. However, corneal transplants, including lamellar strategies, have their own set of challenges, such as graft rejection, delayed graft failure, shortage of donor corneas, repeated treatments, and post-surgical complications. Corneal defects and diseases are one of the leading causes of blindness globally; therefore, there is a need for gene-based interventions that may mitigate some of these challenges and help reduce the burden of blindness. Corneas being immune-advantaged, uniquely avascular, and transparent is ideal for gene therapy approaches. Well-established corneal surgical techniques as well as their ease of accessibility for examination and manipulation makes corneas suitable for in vivo and ex vivo gene therapy. In this review, we focus on the most recent advances in the area of corneal regeneration using gene therapy and on the strategies involved in the development of such therapies. We also discuss the challenges and potential of gene therapy for the treatment of corneal diseases. Additionally, we discuss the translational aspects of gene therapy, including different types of vectors, particularly focusing on recombinant AAV that may help advance targeted therapeutics for corneal defects and diseases.

The endocrine system influences all tissues and cells in the human body. The ocular surface is constantly exposed to circulating hormones and expresses their specific receptors. Dry eye disease (DED) is a disorder with multifactorial etiology, and endocrine anomalies are one of the inciting factors. The endocrine anomalies that cause DED include physiological conditions such as menopause, menstrual cycle variations, pathologies such as polycystic ovarian syndrome, androgen resistance, iatrogenic conditions such as contraceptive use, and antiandrogen treatment. This review highlights the status of these hormones in DED along with the mechanism of action of different hormones on the ocular surface structures and the clinical implications of these effects. The influence of androgens, estrogens, and progesterone on the ocular surface tissues, and the implications of androgen-deficient states in DED are also discussed. The physiological and pathological effects of menopause and sex hormone replacement therapy are discussed. The effects of insulin and insulin resistance on the ocular surface and DED, and the growing potential of topical insulin therapeutics for DED are mentioned. Thyroid-associated ophthalmopathy, its impact on the ocular surface, and the tissue effects of thyroid hormone in the context of DED are reviewed. Finally, the potential role of hormonal therapeutics in the management of DED has also been discussed. The compelling evidence suggests that it would be clinically beneficial to consider the possibility of hormonal imbalances and their impact while treating patients with DED.

Dry eye disease (DED) is a commonly occurring, multifactorial disease characterized by reduced tear film stability and hyperosmolarity at the ocular surface, leading to discomfort and visual compromise. DED is driven by chronic inflammation and its pathogenesis involves multiple ocular surface structures such as the cornea, conjunctiva, lacrimal glands, and meibomian glands. The tear film secretion and its composition are regulated by the ocular surface in orchestration with the environment and bodily cues. Thus, any dysregulation in ocular surface homeostasis causes an increase in tear break-up time (TBUT), osmolarity changes, and reduction in tear film volume, all of which are indicators of DED. Tear film abnormalities are perpetuated by underlying inflammatory signaling and secretion of inflammatory factors, leading to the recruitment of immune cells and clinical pathology. Tear-soluble factors such as cytokines and chemokines are the best surrogate markers of disease severity and can also drive the altered profile of ocular surface cells contributing to the disease. Soluble factors can thus help in disease classification and planning treatment strategies. Our analysis suggests increased levels of cytokines namely interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-9, IL-12, IL-17A, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α); chemokines (CCL2, CCL3, CCL4, CXCL8); MMP-9, FGF, VEGF-A; soluble receptors (sICAM-1, sTNFR1), neurotrophic factors (NGF, substance P, serotonin) and IL1RA and reduced levels of IL-7, IL-17F, CXCL1, CXCL10, EGF and lactoferrin in DED. Due to the non-invasive sample collection and ease of quantitively measuring soluble factors, tears are one of the best-studied biological samples to molecularly stratify DED patients and monitor their response to therapy. In this review, we evaluate and summarize the soluble factors profiles in DED patients from the studies conducted over the past decade and across various patient groups and etiologies. The use of biomarker testing in clinical settings will aid in the advancement of personalized medicine and represents the next step in managing DED.