Medical hypothesis, discovery & innovation in optometry

Background: Keratoconus is a progressive corneal ectatic disorder characterized by stromal thinning, corneal protrusion, and progressive visual impairment. Corneal collagen cross-linking (CXL) is an established treatment for halting disease progression by enhancing corneal biomechanical stability. This study evaluated early corneal structural and functional changes following accelerated epithelium-off CXL in eyes with progressive keratoconus using anterior segment optical coherence tomography (AS-OCT). Specifically, epithelial thickness and central corneal thickness (CCT) were assessed one month after treatment and correlated with stromal demarcation line depth.
Methods: In this prospective study, eyes with progressive keratoconus underwent accelerated epithelium-off CXL. All participants underwent comprehensive ophthalmic examination before treatment and one month postoperatively. Assessments included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), intraocular pressure (IOP), corneal tomographic parameters, CCT, epithelial thickness, and AS-OCT measurement of stromal demarcation line depth.
Results: Thirty eyes of 15 patients with progressive keratoconus underwent accelerated epithelium-off CXL. Mean (standard deviation) age of participants was 26.5 (4.5) years (range 19–35), and 53.3% (n = 8) were female. At one month, modest but statistically significant improvements were observed in both UDVA and CDVA (both P < 0.05). A slight but statistically significant reduction in IOP was also observed (P < 0.05). Keratometric parameters yielded modest but significant reductions following treatment (all P < 0.05), consistent with early corneal flattening. Significant decreases were observed in both CCT and epithelial thickness (both P < 0.05). The median (interquartile range) stromal demarcation line depth measured by AS-OCT was 214.5 (171.0–274.3) micrometre, with 143–322 micrometre value ranges. Demarcation line depth showed significant positive correlations with both preoperative CCT (rho = 0.368, P = 0.045) and postoperative CCT (rho = 0.433, P = 0.017), whereas no significant associations were observed with preoperative (rho = -0.197, P = 0.298) or postoperative (rho = -0.093, P = 0.625) epithelial thickness.
Conclusions: Accelerated epithelium-off CXL was associated with early corneal structural changes, including reductions in CCT and epithelial thickness, accompanied by mild corneal flattening and modest improvements in visual acuity. Stromal demarcation line depth was positively correlated with CCT, suggesting an association between corneal thickness and treatment penetration. AS-OCT provided detailed, non-invasive assessment of postoperative demarcation line depth and may serve as a useful tool for monitoring early response to CXL. Further studies with larger sample sizes, longer follow-up periods, and multicenter recruitment are warranted to validate these findings in our population.

Background: Customized corneal cross-linking (CXL) enables spatially individualized ultraviolet-A (UVA) irradiation of ectatic corneas. However, changes in the thickness and spatial location of the thinnest corneal point remain insufficiently characterized. This study evaluated 1-year changes in these parameters following customized epithelium-off CXL for progressive corneal ectasia. Secondary aims were to assess keratometric, visual, refractive, and corneal aberrometric outcomes and correlations of age with baseline, 1-year postoperative, and longitudinal changes in thinnest-point location and pachymetry.
Methods: This retrospective interventional case series consecutively included patients with progressive corneal ectasia who underwent customized epithelium-off CXL and completed 1-year follow-up. Treatment was performed using the Mosaic platform with individualized spatial irradiation patterns planned from preoperative tomographic maps. The treatment pattern was geometrically centred on the pupil, with a patient-specific offset derived from the x- and y-coordinates of the thinnest corneal point to target the ectatic region using spatially graded UVA irradiation. Corneal pachymetry and thinnest-point x- and y-coordinates were measured with the Sirius 3D Corneal Topographer at baseline and 1 year. Secondary outcomes included maximum keratometry (Kmax), mean keratometry (Kmean), corrected and uncorrected distance visual acuity (CDVA and UDVA), refractive astigmatism, and total coma.
Results: The study included 32 eyes of 23 patients: 12 men (52.2%) and 11 women (47.8%), with a mean (standard deviation [SD]) age of 24.39 (4.13) years (range, 19–34). Twenty-eight eyes (87.5%) had keratoconus and 4 (12.5%) had post-LASIK ectasia. Mean (SD) thinnest corneal thickness decreased significantly from 442.28 (31.09) micrometre preoperatively to 405.75 (29.71) micrometre at 1 year (P < 0.001), with no significant changes in the x- or y-coordinates of the thinnest corneal point (both P > 0.05). Significant reductions occurred in Kmax, Kmean, CDVA, and total coma (all P < 0.05), whereas UDVA and refractive astigmatism did not change significantly (both P > 0.05). Age was not significantly correlated with preoperative or 1-year x- or y-coordinates or with preoperative or postoperative thinnest corneal thickness (all P > 0.05). A moderate positive correlation with change in the y-coordinate (r = + 0.444; P < 0.05) was not retained after adjustment for within-subject inter-eye correlation using a mixed-effects model (P > 0.05).
Conclusions: Customized epithelium-off CXL was associated with significant 1-year reductions in thinnest corneal thickness and corneal steepness, improvements in selected visual and aberrometric outcomes, and stable thinnest-point location. Larger prospective controlled studies with longer follow-up are needed to determine the durability and clinical significance of these structural changes.

Background: Accurate objective assessment of refractive error is essential for efficient clinical refraction and optimal spectacle prescription, particularly with the growing use of wavefront-based technologies in contemporary ophthalmic practice. We aimed to compare refractive measurements obtained by subjective refraction, conventional autorefractometry, Hartmann-Shack wavefront aberrometry (WASCA), and ray-tracing wavefront aberrometry (iTrace) in healthy young adults, and to evaluate the suitability of each objective modality as a starting point for subjective refraction.
Methods: This study included healthy adults aged 18–30 years, recruited at Nethradhama Superspeciality Eye Hospital, Bengaluru, India, between October 2021 and June 2022. Participants underwent comprehensive ophthalmic examination followed by refractive assessment using subjective refraction, autorefractometry, WASCA Hartmann-Shack wavefront aberrometry, and iTrace ray-tracing wavefront aberrometry under non-cycloplegic conditions. Spherical equivalent (SE) measurements obtained by the four modalities were compared using repeated measures analysis of variance with Tukey honestly significant difference post hoc testing. A one-sample t-test was used to determine whether the mean difference between subjective refraction and autorefractometry differed significantly from zero.
Results: The study cohort comprised 60 healthy adults (120 eyes) aged 18–30 years, 24 males (40%) and 36 females (60%), with a mean (standard deviation [SD]) age of 21.4 (1.4) years. Significant differences in SE measurements were observed among the four modalities for both right eyes (RE) and left eyes (LE) (both P < 0.05). In the RE, mean (SD) SE values were -0.65 (0.81) D for subjective refraction, -0.74 (0.89) D for autorefractometry, -0.98 (0.88) D for WASCA, and -1.15 (1.26) D for iTrace. Corresponding LE values were -0.54 (0.92) D, -0.67 (0.79) D, -0.94 (0.84) D, and -1.24 (0.97) D, respectively. Post hoc analysis revealed significant differences between subjective refraction and both WASCA and iTrace measurements in both eyes (all P < 0.05), whereas differences between subjective refraction and autorefractometry were not statistically significant (both RE and LE P > 0.05). The mean inter-method difference between subjective refraction and autorefractometry differed significantly from zero in both eyes (RE: 0.09 [0.32] D, LE: -0.13 [0.50] D; both P < 0.05).
Conclusions: Autorefractometry produced refractive measurements that were closer to subjective manifest refraction than those obtained with either Hartmann-Shack or ray-tracing wavefront aberrometry. Both aberrometers displayed a tendency toward more myopic refractive estimates. Although autorefractometry remains a practical and reliable objective starting point for subjective refraction, subjective refraction continues to represent the reference standard for final spectacle prescription.

Background: Botulinum toxin injection is the most widely performed nonsurgical procedure for upper facial rejuvenation and has an established safety profile. However, because the lacrimal gland is anatomically supported by the surrounding periorbital soft tissues, temporary muscle relaxation following periorbital botulinum toxin injection may alter its position. This prospective pilot study investigated changes in lacrimal gland position after cosmetic periorbital botulinum toxin injection using standardized ultrasonographic measurements.
Methods: This prospective pilot study enrolled eligible adults undergoing cosmetic periorbital botulinum toxin type A injection at a tertiary ophthalmic center between January 2022 and September 2024. Participants underwent standardized ophthalmic and periorbital examinations before treatment. Lacrimal gland ultrasonography was performed at baseline and two weeks after injection by a blinded radiologist in both the supine and sitting positions. Maximum axial and anteroposterior diameters of both lacrimal glands were measured bilaterally. Changes from baseline, group comparisons, and associations with demographic and clinical characteristics were evaluated.
Results: Nineteen participants (10 [52.6%] women and 9 [47.4%] men; mean [standard deviation] age, 45.3 [9.0] years) were included. Compared with baseline, lacrimal gland dimensions generally increased after periorbital botulinum toxin injection, except for a small, non-significant decrease in the axial diameter of the right lacrimal gland in the supine position (P > 0.05). Statistically significant increases in both axial and anteroposterior diameters of the right and left lacrimal glands were observed in the sitting position (all P < 0.05), whereas no significant changes were detected in the supine position (all P > 0.05). Changes in ultrasound parameters were not associated with age, sex, previous upper-eyelid blepharoplasty, or the number of crow's-feet injection points (all P > 0.05).
Conclusions: This prospective pilot study demonstrated that cosmetic periorbital botulinum toxin injection was associated with ultrasonographic changes consistent with altered position of the lacrimal gland in the sitting position, whereas no significant changes were observed in the supine position. These findings suggest that temporary relaxation of the periorbital musculature may influence lacrimal gland position. Larger prospective studies with longer follow-up and comprehensive functional assessments are warranted to verify these preliminary findings and clarify their clinical significance.

Background: Artificial intelligence (AI) is increasingly being incorporated into ophthalmic practice and shows promise in improving diagnostic accuracy, patient selection, surgical planning, and postoperative care. In corneal transplantation, AI-based tools may help clinicians make more informed decisions throughout the patient journey. This review examines the current evidence on the use of AI in corneal transplantation, with a focus on its clinical applications, existing challenges, and future potential for routine practice.
Methods: A literature review was conducted to identify studies evaluating the use of AI in corneal transplantation. Searches were conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases for articles published up to 20 August 2025. The search strategy combined terms related to “artificial intelligence”, “machine learning”, and “deep learning” with “corneal transplantation” and “keratoplasty”.
Results: Twenty studies met the inclusion criteria. Most studies used imaging modalities such as anterior segment optical coherence tomography (AS-OCT), specular microscopy, or surgical videos, while others incorporated structured clinical information or multimodal datasets. Descemet membrane endothelial keratoplasty (DMEK) was the most commonly investigated procedure. AI approaches predominantly utilized supervised methodologies, spanning deep learning networks and traditional machine learning algorithms alongside a limited application of unsupervised and survival-based models. Common objectives included predicting graft outcomes, detecting and quantifying graft detachment, identifying factors associated with graft failure, and assisting surgical decision-making. Classification and image segmentation were the predominant analytical tasks. AI models evidenced favorable predictive and analytical performance across a broad range of clinical applications, highlighting their potential to support preoperative risk stratification, intraoperative decision-making, postoperative monitoring, and long-term graft outcome prediction.
Conclusions: The current literature suggests that AI has the potential to become an important clinical support tool in corneal transplantation. By integrating imaging, biometric, and clinical data, AI models may help predict graft survival, identify patients at higher risk of complications, and facilitate more personalized management strategies. Although the reported results are encouraging, several barriers remain, including limited external validation, lack of standardized datasets, and concerns about model interpretability. Future work should focus on developing robust, explainable, and generalizable AI systems through multicenter collaboration and multimodal data integration to support their safe and effective adoption in clinical practice.

Background: Vitamins are essential for ocular health, and their deficiencies are associated with xerophthalmia, age-related macular degeneration (AMD), cataracts, glaucoma, diabetic retinopathy (DR), dry eye disease (DED), keratoconus, and optic neuropathies. Beyond preventing nutritional deficiency disorders, vitamins contribute to phototransduction, antioxidant defense, immune regulation, and maintenance of retinal, corneal, and optic nerve function. This narrative review summarizes current evidence on the role of individual vitamins in ocular health, highlights clinical findings, and identifies research gaps.
Methods: A targeted search of PubMed/MEDLINE and Google Scholar was conducted for English-language studies published between 2000 and 2025. Keywords included “vitamins”, “ocular health”, “eye disease”, “antioxidants”, “retina”, “cornea”, and “nutritional deficiency”. Relevant clinical trials, observational studies, reviews, and guidelines were included. Non-English-language studies and unrelated nutritional research were excluded.
Results: Vitamin A is crucial for phototransduction and epithelial integrity; deficiency leads to night blindness, xerophthalmia, and corneal disease. B-complex vitamins, particularly B1, B2, B6, B12, and folate, are associated with neuro-ophthalmic function, retinal vascular health, and homocysteine metabolism. Vitamin C, a potent antioxidant, protects against oxidative damage in the lens and retina and promotes corneal wound healing. Vitamin D demonstrates emerging therapeutic potential in DED, glaucoma, DR, keratoconus, and AMD through its anti-inflammatory, antioxidant, neuroprotective, and anti-angiogenic properties. Vitamin E contributes to retinal protection and slowing progression of AMD through its antioxidant activity. Additional evidence supports the complementary role of lutein, zeaxanthin, omega-3 fatty acids, and zinc in maintaining retinal integrity and ocular surface health. Deficiencies, malabsorption syndromes, aging, and poor dietary habits contribute significantly to ocular morbidities linked with hypovitaminosis.
Conclusions: Adequate intake of vitamins and selected micronutrients is essential for ocular surface maintenance, retinal function, optic nerve health, and protection against oxidative stress-related diseases. Nutritional assessment and targeted supplementation, particularly in high-risk populations, may help prevent or delay the onset and progression of major eye diseases. Further large-scale randomized controlled trials are warranted to establish evidence-based therapeutic guidelines and optimal supplementation strategies.