Medical Hypothesis, Discovery & Innovation (MEHDI) Ophthalmology Journal
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Role of reactive oxygen species and oxidative stress in the pathomechanism of glaucoma
Full text linkBackground: Glaucoma is a major cause of vision impairment and blindness, characterized by damage to retinal ganglion cells (RGC) at the optic nerve head (ONH). The pathomechanism underlying glaucoma is heterogeneous and theories explaining the pathomechanism can be categorized as mechanical, vascular, or immunological. This mini-review explores the involvement of reactive oxygen species (ROS) and oxidative stress in these established mechanisms of glaucoma.
Methods: A review of literature was conducted using PubMed/MEDLINE, with the query including the following keywords: “antioxidants”, “glaucoma”, “glaucoma pathomechanism”, “immunological”, “intraocular pressure”, “mechanical”, “reactive oxygen species”, “ocular hypertension”, “oxidative stress”, and “vascular”. The date filter was set from January 2010 to September 2025. Papers that were relevant to ROS or oxidative stress in the glaucoma pathomechanism were thoroughly reviewed. Their reference lists were also reviewed for relevant papers of any date.
Results: Following a comprehensive literature search, 67 journal articles were selected for review. They revealed the role of ROS and oxidative stress in the mechanical, vascular, and immunological pathomechanism theories of glaucoma. In the mechanical theory, oxidative stress mediates RGC apoptosis and trabecular meshwork damage. In vascular processes, retinal ischemia causes oxidative stress and vice versa, thus causing RGC death and ONH damage. With the immunological theory, ROS is implicated in glial cell and inflammasome activity that causes RGC injury. Key players in the generation of oxidative stress include NADP oxidase 2, dynamin-related protein 1, mitofusin 2, nuclear factor (erythroid-derived 2) like 2, and nitric oxide. Conversely, various antioxidant factors are also implicated in glaucoma, yet in oxidative stress conditions their effects are outweighed by those of ROS.
Conclusions: ROS and oxidative stress are important mediators in the glaucoma pathomechanism. They contribute to and unify the existing theories of mechanical, vascular, and immunological injury in glaucoma. Investigating specific oxidative stress players in the pathomechanism may reveal new therapeutic targets in the treatment of glaucoma
Pregnancy-related retinal disorders: clinical features, systemic associations, and management insights
Full text linkBackground: Pregnancy induces profound hormonal, hemodynamic, and metabolic changes that can trigger or exacerbate retinal disorders, some of which may signal systemic complications. This narrative review summarizes current knowledge on retinal diseases specifically induced or worsened during pregnancy.
Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Google Scholar up to 31 September 2025, supplemented by manual screening of reference lists of included records. Search terms included “pregnancy”, “preeclampsia”, “eclampsia”, “HELLP syndrome”, “hemolysis, elevated liver enzyme levels, and low platelets syndrome”, “retinal disease”, “retinopathy”, “hypertensive retinopathy”, “serous retinal detachment”, “central serous chorioretinopathy”, “diabetic retinopathy”, “Valsalva retinopathy”, “retinal vein occlusion”, “retinal artery occlusion”, “idiopathic intracranial hypertension”, and “artificial intelligence”. Eligible articles included case reports, case series, observational studies, reviews, and meta-analyses describing retinal conditions specifically induced or worsened during pregnancy. Data were synthesized narratively.
Results: Pregnancy can precipitate sight-threatening retinal pathology or accelerate pre-existing disease. Hypertensive retinopathy associated with preeclampsia and eclampsia is among the most clinically significant conditions, presenting with arteriolar narrowing, retinal hemorrhages, cotton-wool spots, and, in severe cases, serous retinal detachment. Metabolic adaptations, particularly in women with pregestational diabetes, may accelerate the progression of diabetic retinopathy, with some patients advancing from nonproliferative to proliferative stages over short intervals. Pregnancy has also been implicated in serous retinal detachment, central serous chorioretinopathy, Valsalva retinopathy, retinal vascular occlusions, and, less commonly, papilledema secondary to idiopathic intracranial hypertension. These disorders range from transient, self-limited entities to sight-threatening events and often reflect systemic pathology, including preeclampsia, eclampsia, or hypercoagulable states. Optical coherence tomography, optical coherence tomography angiography, and fundus photography provide safe, noninvasive diagnostic and monitoring modalities. Artificial intelligence (AI)-based retinal imaging offers accurate, noninvasive assessment of diabetic and hypertensive retinopathy and demonstrates expert-level performance across clinical settings. Management emphasizes stabilization of maternal systemic disease, optimization of glycemic and blood pressure control, and multidisciplinary care. Most conditions improve postpartum, but prompt recognition is essential to prevent permanent visual loss.
Conclusions: Pregnancy can precipitate or exacerbate a range of retinal disorders, reflecting the complex vascular, hormonal, and metabolic changes of gestation. Noninvasive imaging, interdisciplinary collaboration, and vigilant monitoring are essential to optimizing maternal and fetal outcomes. Awareness and early detection of pregnancy-associated retinal disorders, together with emerging AI-based tools, may further improve outcomes. Longitudinal studies are needed to establish evidence-based screening and management protocols
Depression, anxiety, and stress indicators for patients who are blind or visually impaired
Full text linkBackground: Severe visual impairment is reportedly detrimental to mental health. Blind individuals are expected to have poorer mental health status compared to those with low vision. However, most mental health studies have focused on people with low vision, leaving a substantial gap in our understanding of the mental health status of the blind. Therefore, this study compared the mental health status of individuals with low vision to that of blind individuals.
Methods: This cross-sectional, questionnaire-based investigation involved individuals with low vision or blindness who were registered with the Social Welfare Department, Federal Territory of Kuala Lumpur, Malaysia. Participants were recruited using a simple random sampling method. The medical records of each participant were screened. Participants were individually interviewed, and their socio-demographic details, education level, working status, marital status, type and duration of impairment, and rehabilitation status were collected. Additionally, the Depression, Anxiety, and Stress Scale (DASS-21) was administered to each individual.
Results: Of the 30 participants, 20 (66.7%) had low vision and 10 (33.3%) had blindness, 16 (53.3%) were men, and most participants were single (n = 20, 66.7%). Congenital and acquired causes of visual impairment each accounted for 50% of cases. Most participants (n = 26, 86.7%) had not received psychosocial rehabilitation. The mean DASS-21 scores for the depression, anxiety, and stress subscales were significantly higher in patients with low vision than in those with blindness (all P < 0.05). Considering the clinical cut-off increments to determine emotional states for the DASS-21 subscales, individuals with low vision were in the mild, moderate, and mild categories for the depression, anxiety, and stress subscales, respectively. Individuals with blindness were categorized as normal in all subscales. The mean DASS-21 scores for the depression, anxiety, and stress subscales among individuals with congenital and acquired causes of visual impairment were comparable (all P > 0.05). Individuals with congenital visual impairment were in the normal, moderate, and normal categories for the depression, anxiety, and stress subscales, respectively. Those with acquired visual impairment were categorized as mild, moderate, and normal for the depression, anxiety, and stress subscales, respectively.
Conclusions: Individuals with low vision experienced mild to moderate levels of mental health issues, which may consist of depression, anxiety, stress, or a combination of these. The blind individuals in this study demonstrated no similar mental health issues. The small number of participants in certain racial and age groups prevents us from concluding how these factors might influence mental health. Further research with a larger sample size should consider the severity of visual impairment, age groups, and ethnicity, as these factors may impact the outcomes
Dynamic changes in tear film parameters after upper eyelid blepharoplasty measured with anterior segment optical coherence tomography
Full text linkBackground: Upper eyelid blepharoplasty, a corrective procedure for dermatochalasis, may transiently affect eyelid function and tear film stability. This study assessed the effect of upper eyelid blepharoplasty, subjectively through questionnaires, and objectively through tear film stability and production.
Methods: This non-randomized, prospective, interventional study consecutively recruited the right eyes of patients with dermatochalasis who underwent bilateral upper eyelid blepharoplasty at a tertiary center. Preoperative assessments included a standardized ophthalmic examination, ocular surface disease index (OSDI) questionnaire, Schirmer’s test I, tear break-up time (TBUT) test, and anterior segment optical coherence tomography (AS-OCT) to measure tear meniscus height (TMH) and tear meniscus area (TMA). Postoperative evaluations were conducted at 1, 3, and 6 months. At the final follow-up, scar quality and patient satisfaction were assessed using the Patient and Observer Scar Assessment Scale.
Results: Fifty eyes of 50 patients with a mean (standard deviation) age of 47.1 (1.6) years were included. Statistically significant postoperative changes were observed in the OSDI score, Schirmer’s test value, TBUT, and TMH at the 6-month follow-up (all P < 0.001). These parameters initially worsened at 1 month and then improved significantly at 3 and 6 months, returning to or surpassing baseline levels. TMA showed a transient postoperative decline, with full recovery at 6 months. Exceptionally strong positive correlations were found between TMH or TMA and TBUT or the Schirmer’s test value at most follow-up visits (all P > 0.05). Patient satisfaction was high, with 95% reporting satisfaction with cosmetic outcomes, and no cases of visible or hypertrophic scarring were observed at final follow-up.
Conclusions: We observed significant yet transient changes in tear film parameters and subjective assessments following upper eyelid blepharoplasty. A strong correlation was observed between AS-OCT measurements and parameters of tear film stability and production. High patient satisfaction and favorable cosmetic outcomes, with no visible scarring, further support the safety and tolerability of this procedure. Further studies with larger cohorts, longer follow-up periods, and comparative designs are warranted to validate these findings and further explore the long-term effects on ocular surface health and patient-reported outcomes
Visual and keratometric outcomes following corneal collagen cross-linking in keratoconus: an experience from Nepal
Full text linkBackground: Keratoconus is a progressive corneal ectasia causing visual impairment, often initially managed using spectacles or rigid gas permeable contact lenses, which do not halt disease progression. Corneal collagen cross-linking (CXL) is the only treatment proven to stabilize the condition. Although its efficacy is well documented globally, data from Nepal are limited. This study evaluated visual and keratometric parameters before and after CXL in Nepali patients with varying severities of keratoconus.
Methods: This retrospective, hospital-based study analyzed visual acuity and keratometric outcomes in patients with keratoconus who underwent epithelium-off CXL at Biratnagar Eye Hospital, Biratnagar, Nepal, between January 2019 and March 2023. Secondary data were extracted from medical records. Only eyes with minimum corneal thickness greater than or equal to 400 µm were included. Patients were classified into Amsler–Krumeich stages I–IV. Pre- and 1-month post-CXL assessments included uncorrected and best-corrected distance visual acuity (UCDVA and BCDVA, respectively) both recorded in logarithm of the minimum angle of resolution, keratometry, slit-lamp biomicroscopy, corneal topography, and fundus evaluation.
Results: A total of 195 eyes from 106 patients with keratoconus were analyzed; 84.0% (n = 89) underwent bilateral CXL. The mean (standard deviation [SD]) age was 19.4 (4.9) years, with most (n = 43, 40.6%) aged 16–20 years. Male patients comprised 71.7% (n = 76) of the cohort. The mean (SD) follow-up duration after CXL was 7.5 (2.6) months. Following CXL, overall BCDVA improved, with statistically significant gains in stages I and IV (both P < 0.05). UCDVA significantly improved in stage II (P < 0.05). In stage I and II eyes, the average keratometry became flatter by –0.4 D and –0.2 D, respectively (both P < 0.05). The mean average keratometry remained comparable to baseline in stage III and IV eyes (both P > 0.05).
Conclusions: CXL is effective in stabilizing keratoconus in Nepali patients, particularly in early stages. Significant improvements in BCDVA, as well as keratometric flattening, were observed in stage I and IV and in stage I and II eyes, respectively. Although advanced-stage eyes (III and IV) showed keratometric stability without significant flattening, the results suggest that CXL can slow or halt disease progression even in later stages. These findings highlight the importance of early diagnosis and timely intervention. Further prospective, multicenter studies are warranted to optimize treatment protocols and expand the understanding of CXL outcomes in this patient population
Curcumin in ocular diseases: therapeutic potential, mechanisms of action, and innovative delivery systems
Full text linkBackground: Curcumin, a natural polyphenol derived from Curcuma longa L., has gained considerable attention in ophthalmology because of its potent anti-inflammatory, antioxidant, and immunomodulatory properties. This review evaluates the therapeutic potential of curcumin in ocular diseases and explores innovative strategies to enhance its bioavailability.
Methods: A comprehensive search was conducted in four major electronic databases—PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar—using keywords related to curcumin, ophthalmology, and drug delivery systems. Studies published in English up to March 10, 2025, were included. Relevant articles were selected based on their focus on the therapeutic effects of curcumin and the application of advanced delivery methods.
Results: Curcumin shows promising therapeutic potential in various ocular conditions due to its anti-inflammatory, antioxidant, and anti-angiogenic properties. Studies highlight its beneficial effects in corneal neovascularization, promoting corneal wound healing, and dry eye disease. It also demonstrates efficacy against allergic and bacterial conjunctivitis, pterygium recurrence, anterior uveitis, and cataracts. Moreover, curcumin may be beneficial in glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy, offering a multi-targeted approach to preserving vision and ocular health. However, its poor bioavailability remains a major limitation. Strategies to overcome this challenge include the development of structural analogs, bioavailability enhancers, and advanced drug delivery systems such as nanoparticles, liposomal systems, micelles, hydrogel-based systems, and nanoemulsions, all of which may enhance the stability, bioavailability, and controlled release of curcumin.
Conclusions: Curcumin has garnered attention in ophthalmology because of its multifaceted therapeutic properties, including anti-inflammatory, antioxidant, apoptosis regulating, antibacterial, and immunomodulatory actions. These properties have demonstrated promising results, highlighting the potential of curcumin in treating various ophthalmic conditions. Despite the promising potential of curcumin in ophthalmic therapies, addressing its poor bioavailability by using innovative drug delivery systems is crucial for maximizing its clinical efficacy. To address these challenges, substantial research has focused on enhancing the bioavailability of curcumin through the development of structural analogs, bioavailability enhancers, and advanced drug delivery systems. Innovative formulations, including nanoparticles, liposomal systems, micellar solutions, hydrogel-based systems, nanoemulsions, microspheres, and transferosomes, are promising approaches to improve the stability, bioavailability, and controlled release of curcumin, offering a hopeful avenue for its future application in ocular therapies
Persistent corneal epithelial defects: an updated review of literature
Full text linkBackground: Persistent corneal epithelial defects (PCEDs) represent a significant clinical challenge characterized by the failure of the corneal epithelium to heal within the normal period, leading to potential sight-threatening complications. These defects arise from a variety of underlying etiologies, including limbal stem cell deficiency, neurotrophic keratopathy, dry eye syndrome, and systemic diseases such as diabetes mellitus. Despite advances in ophthalmic care, PCEDs remain difficult to treat due to diverse pathophysiological mechanisms and variable response to conventional therapies. Recent developments in growth factor therapies, biological treatments, surgical techniques, and regenerative medicine have expanded therapeutic options but necessitate comprehensive review to guide clinical practice.
Methods: A comprehensive narrative review was conducted through a systematic search of major electronic databases including PubMed/MEDLINE, Embase, Scopus, and Google Scholar. The search incorporated keywords and Medical Subject Headings related to “persistent corneal epithelial defects”, “corneal epithelial healing”, “limbal stem cell deficiency”, “neurotrophic keratopathy”, “amniotic membrane transplantation”, and “emerging treatments”. Peer-reviewed original studies, clinical trials, reviews, and meta-analyses published between 1 January 2000 and 31 March 2025 were included. Articles were critically appraised and selected according to their relevance, methodological quality, and contribution to understanding PCED pathophysiology, diagnosis, and treatment advancements.
Results: The review delineates the anatomy and physiological roles of the corneal epithelium, highlighting mechanisms that lead to epithelial defect persistence, including impaired basement membrane integrity, stem cell deficiency, inflammation, and neurotrophic factors. Clinical presentation and diagnostic modalities such as fluorescein staining and advanced imaging techniques are discussed. Standard management with lubricants, therapeutic contact lenses, infection control, and autologous serum eye drops is described, alongside medical therapies targeting epithelial regeneration, including recombinant human nerve growth factor and platelet-rich plasma. Surgical interventions like amniotic membrane transplantation and novel regenerative approaches involving stem cell therapy and corneal neurotization show promising results in refractory cases. Emerging molecular therapies and bioengineered drug delivery systems represent the forefront of innovation in PCED treatment.
Conclusion: PCEDs pose complex therapeutic challenges necessitating a multifaceted treatment approach. Advances in molecular, cellular, and surgical therapies have substantially expanded management options and improved healing outcomes. However, continued research into personalized therapies, optimization of delivery methods, and long-term safety is essential. This review provides a comprehensive synthesis of current knowledge and emerging trends to inform clinicians and researchers in the effective management of PCEDs, ultimately aiming to preserve vision and enhance quality of life. Future research should focus on minimally invasive sustained-release therapies, biomarker-guided personalized interventions, and combination approaches targeting epithelium, inflammation, and nerves.
 
Vascular supply of the eye: clinical anatomy
Full text linkBackground: Eye function is vitally dependent on an adequate blood supply, primarily provided by the ophthalmic artery, an internal carotid artery branch. This review provides an overview of the vascular supply of the eye.
Methods: A targeted search of PubMed / MEDLINE was performed using the terms “central retinal vein,” “central retinal artery,” “internal carotid artery,” “ophthalmic artery,” “ophthalmic vein,” “posterior ciliary arteries,” “retinal capillaries,” “vascular supply of the eye,” “ocular vascular supply,” “external carotid artery,” and “vortex vein”. Studies published between 1960 and 2024 were reviewed. Relevant references cited in these publications were also analyzed.
Results: Overall, 62 publications were reviewed. The ophthalmic artery branches into several arteries—the central retinal artery supplies the retina, whereas the posterior ciliary arteries supply the posterior choroid and optic nerve. The anterior ciliary arteries mainly supply the conjunctiva, sclera, ciliary body, and iris. Extraocular muscles receive their primary blood supply from the muscular branches of the ophthalmic artery, lacrimal artery, and infraorbital artery. The lacrimal gland is perfused by the lacrimal artery. The eyelids receive blood from both the internal and external carotid arteries. The superficial vascular network of the medial eyelid skin is established primarily through anastomoses between the branches of the internal carotid artery. The superficial vascular network of the lateral upper and lower eyelids is primarily derived from branches emanating from the superficial temporal artery (a branch of the external carotid artery) and the lacrimal artery. Venous drainage follows a complex pathway, beginning with the central retinal vein and the vortex veins, then draining into the ophthalmic veins, and finally into the internal jugular vein.
Conclusions: The eye features a complex arterial supply and venous drainage that can vary greatly among individuals. This complex vascular system is critical for the oxygenation and nutrition of ocular tissues and the maintenance of ocular health. The arterial and venous circulation coordinate to support different regions of the eye, including the retina, choroid, and optic nerve. Understanding this intricate vascular network is essential for the diagnosis and treatment of various ocular pathologies. Abnormalities in these pathways can cause substantial problems, including vision loss
Grading scales for vitreous haze
Full text linkBackground: Grading scales for vitreous haze are crucial for the diagnosis, monitoring, and management of uveitis. The presence of inflammatory cells within the vitreous cavity is widely recognized as a key indicator of disease activity and severity, offering valuable insights into the underlying inflammatory processes. This mini-review aims to explore the evolution of vitreous haze grading scales systematically, emphasizing conventional grading methods, advances in imaging technologies, and the integration of artificial intelligence (AI) into the grading process.
Methods: The PubMed/MEDLINE database was comprehensively searched for studies published between 1959 and 2024, using keywords such as “AI-based grading systems,” “artificial intelligence,” “automated grading,” “grading scales for vitreous cells,” “inflammation,” “uveitis,” and “vitreous haze.” Relevant studies were identified, and additional articles were selected by reviewing the reference lists of the included publications. The selection of articles for inclusion in the mini-review was limited to those written in English.
Results: In the current literature, two grading methods are used: the National Institutes of Health (NIH) scale and the Miami scale. Despite their widespread utilization, both scales entail subjective assessments of vitreous haze, which renders them susceptible to observer bias and interobserver variability. The NIH scale uses six levels, while the Miami scale employs nine levels, both of which require subjective assessments of vitreous haze. Recent advances in objective imaging technologies, namely ultrawide-field fundus photography and advanced optical coherence tomography-based analysis, have given rise to increasingly consistent and standardized grading systems, which may enhance the reliability of these assessments. Innovative techniques have been developed to enhance accuracy and sensitivity, thereby facilitating the early detection and precise monitoring of vitreous inflammation. Despite these advances, challenges remain, including the difficulty of distinguishing subtle variations in vitreous haze and the variability of inflammatory presentations. The incorporation of AI-driven tools and state-of-the-art imaging technologies into the vitreous cell grading signifies a substantial advance in the evaluation and management of uveitis.
Conclusions: The development of more objective, reproducible, and quantitative grading scales is imperative for optimizing uveitis evaluation and grading vitreous haze in clinical settings and clinical trials. These innovations will also provide robust endpoints for clinical studies, ultimately improving patient care. Moreover, objective grading criteria will enhance diagnostic precision, facilitate better management of ocular inflammatory diseases, and promote further advances in uveitis research and treatment
Anti-vascular endothelial growth factor therapies in ophthalmology
Full text linkBackground: Retinal diseases, including neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion, are leading causes of vision loss worldwide. The introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies has dramatically changed the management of these conditions, offering targeted treatment that can preserve and even improve vision. We aimed to provide a comprehensive review of the development, clinical applications, and emerging indications of anti-VEGF therapies in ophthalmology, including biosimilar agents.
Methods: A comprehensive literature search was conducted in PubMed/MEDLINE for English-language articles published up to 31 July 2025. Additional sources were identified through manual screening of reference lists. Included studies spanned various designs: clinical trials, meta-analyses, observational studies, and preclinical research. Keywords used in the search strategy included terms such as “anti-VEGF therapy”, “biosimilar pharmaceuticals”, “intravitreal and intrastromal anti-VEGF injections”, “retinal diseases” including “macular degeneration” and “retinal neovascularization”, “ranibizumab”, and “bevacizumab”, as well as relevant MeSH terms where applicable.
Results: Anti-VEGF agents have transformed the management of retinal diseases such as neovascular age-related macular degeneration, diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Newer agents such as brolucizumab and faricimab offer prolonged durability and enhanced anatomic outcomes, while biosimilars provide cost-effective alternatives. Anti-VEGF therapy has also shown promise in off-label or emerging indications such as neovascular glaucoma, corneal neovascularization, and other retinal or choroidal disorders including secondary macular edema and/or macular neovascularization associated with various forms of uveitis, diffuse choroidal hemangioma in Sturge-Weber Syndrome, hereditary retinal disorders such as fundus flavimaculatus, Coats-Like retinitis pigmentosa, Peripherin-2-associated retinopathy, immune checkpoint inhibitor use, radiation retinopathy, retinitis pigmentosa, Bietti crystalline dystrophy, autosomal recessive bestrophinopathy, melanocytoma-associated macular neovascular membrane, Best disease, Wyburn-Mason syndrome, choroidal osteoma, peripheral exudative hemorrhagic chorioretinopathy, traumatic choroidal rupture, torpedo maculopathy, optic disc melanocytoma, type 2 proliferative macular telangiectasia, and Coats disease. High-dose formulations and innovative delivery systems are under active investigation to reduce the treatment burden and extend dosing intervals.
Conclusions: Anti-VEGF therapies have revolutionized the field of ophthalmology, providing sight-saving treatment for a range of retinal diseases that were once considered untreatable or inevitably blinding. Today, anti-VEGF drugs are the go-to option for managing neovascular retinal disorders, thanks to their proven efficacy, favorable safety profile, and transformative impact on modern eye care