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Open research questions in Glaucoma and retinal disorders

38 unresolved questions extracted from the limitations and future-work sections of 388 Glaucoma and retinal disorders papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Although single-response evaluation better reflects routine clinical use, response consistency across repeated prompts warrants further investigation. Fourth, confidence scores or probabilistic outputs were not requested, and therefore confidence-based metrics such as AUROC and AUPRC could not be evaluated.

    Comparative performance of chatgpt and gemini in diagnostic classification and clinical reasoning for open-angle glaucoma: a standardized scenario-based study · 2026 · DOI

  • leaders; messages 1. Ensure sustained rural glaucoma education through primary health-care clinics, churches, markets, radio & community include: asymptomatic disease, family history, age > 40 years, regular examination. Incorporate opportunistic glaucoma-risk education and referral into hypertension and diabetes clinics to identify adults with appropriate comorbidities. should 2. 3. Conduct screening outreach and outreach services with a clear referral and follow-up process at regular intervals, particularly in rural areas where eye care services are less readily available. 4. Minimize financial and travel restrictions by providing subsidized screening, travel assistance (where possible), and better co-ordination between primary and specialist eye services. 5. Reduce the use of eye drops without supervision by advocacy activities in the community, pharmacy, and patent medicine vendors. survey, explores Related-publication statement A companion manuscript, based on the same cross-sectional community the prevalence and clinical determinants of glaucoma. The present manuscript focused on a different question and provides different findings: glaucoma awareness and knowledge, self-reported risk factors, access to eye care, routine eye-check practices, and barriers to care. Does not replicate prevalence estimates or adjusted determinant analyses that accompany the manuscript and came from a different source.

    Glaucoma Knowledge, Self-Reported Risk Factors, and Eye-Care Access in Selected Rural and Urban Communities of Abia State, Nigeria · 2026 · DOI

  • Randomized controlled trials comparing the iStent infinite device to medical therapy or other micro-invasive glaucoma surgery devices would provide evidence for comparative effectiveness. Follow-up extending 3 to 5 years is essential to assess the durability of intraocular pressure control and determine if effect magnitude is maintained. Studies in diverse populations with varying glaucoma severities, subtypes beyond primary open-angle glaucoma, and different demographic groups would clarify the breadth of appropriate clinical applications.

    Efficacy and Safety of the iStent infinite Trabecular Micro-Bypass Device for Glaucoma: A Systematic Review and Meta-Analysis · 2026 · DOI

  • Future studies are needed to determine the incidence of sequential ODR to CRVO after glaucoma surgery, identify patient- and procedure-related risk factors, and clarify the underlying hemodynamic and structural mechanisms linking these conditions.

    Ocular Decompression Retinopathy Followed by Central Retinal Vein Occlusion After Augmented Trabeculectomy in Pseudoexfoliative Glaucoma: A Case Report · 2026 · DOI

  • Second, the included studies were predominantly non-random- ized studies with small sample sizes, inherent selection bias, and lack of standardized protocols. Sixth, the lack of standardized outcome reporting across studies, particularly regarding complications and quality of life measures, prevented comprehensive synthesis of these impor- tant endpoints (49).

    Cataract and glaucoma surgery in microphthalmic, nanophthalmic, and high hyperopic eyes: a systematic review and meta-analysis · 2026 · DOI

  • This study has several limitations. Firstly, the sample size was relatively small, which limits generalizability. Secondly, all participants were surgical candidates scheduled for trabeculectomy, meaning most had advanced-stage glaucoma; thus, elevated TNF-α levels may reflect a population with more severe disease, introducing selection bias. Thirdly, the cross-sectional design prevents causal inference between TNF-α elevation and RGC damage, allowing only association at a single time point. Fourthly, the absence of a healthy control group limits direct comparison of TNF-α values with those of normal eyes, requiring reliance on literature-based reference values. Finally, other factors that may influence RGC thickness and cytokine expression, such as degree of myopia, axial length, or long-term topical medication use, were not evaluated. Future studies with larger samples, inclusion of normal control groups, and longitudinal designs are needed to validate these findings and further elucidate the mechanistic role of TNF-α in glaucoma progression.

    Association of Aqueous Humor Tumor Necrosis Factor Alpha with Retinal Ganglion Cell Thickness in Juvenile versus Adult-Onset Primary Open-Angle Glaucoma · 2026 · DOI

  • STUDY LIMITATIONS This study has several limitations. Further randomized studies with larger cohorts and extended follow- up are warranted to validate these findings and to better de- fine the role of MIMS in the surgical management of glau- coma [6–8]. Future randomized, controlled studies with larger cohorts and extended follow-up are warranted to confirm these results and better establish the role of MIMS in glaucoma surgery [6–8].

    Minimally invasive micro-sclerostomy (MIMS): a novel approach to lowering intraocular pressure and reducing medication burden · 2026 · DOI

  • essible community settings, its performance under real-world, unsupervised conditions remains to be established. Future studies using the updated MVT-s device, which includes distance feedback based on a time-of-flight sensor, are warranted.

    Tablet-based multi-stimulus perimetry for glaucoma screening · 2026 · DOI

  • Population-based biom- etric data from Southern European and Balkan cataract populations remain limited, and com- prehensive analyses incorporating both biom- etric parameters and astigmatism characteris- tics are scarce [6, 8, 18, 19].

    The Role of Sex in Ocular Biometry: A Large-Scale Study of Cataract Candidates in Greece · 2026 · DOI

  • Background: Peripapillary hyper-reflective ovoid mass-like structures (PHOMS) are commonly observed in optic disc swelling of various etiologies, but the factors contributing to their formation have not been fully elucidated.

    Association Between Peripapillary Hyperreflective Ovoid Mass-Like Structures and Optic Nerve Head Morphology in Eyes With Optic Disc Edema · 2026 · DOI

  • Preclinical studies suggest insulin promotes retinal ganglion cell survival and regeneration, but its safety in higher concentrations (100 and 500 units/mL), administered topically, has been poorly characterized in humans.

    Safety of insulin eye drops in the tratment of open angle glaucoma: a randomized phase I clinical trial · 2026 · DOI

  • Introduction In dogs, intraocular pressure (IOP) responses to topical atropine administration vary, and the anatomical basis for this variability remains unclear.

    Atropine-induced intraocular pressure changes and anterior segment structural parameters in dogs assessed by ultrasound biomicroscopy · 2026 · DOI

  • The current large sample size of visual field findings only included results obtained using SITA-Faster, and thus, different SITA test algorithms could not be compared directly. Rather, previous studies were relied upon, which have documented different variability characteristics comprehensively for the SITA family. Also, multiple results were used from the same subject.

    Clinical Effective Dynamic Range and the Measurement Floor of SITA-Faster Visual Field Tests · 2026 · DOI

  • Several limitations should be acknowledged. First, the relatively modest sample size (n = 24) limits the statistical power of our multivariate regression analyses. Therefore, the results of these models should be interpreted with caution, as the number of variables examined is relatively high relative to the sample size. Future studies with larger cohorts are needed to validate these findings. Second, the single 2-year follow-up precludes assessment of long-term remodeling trajectories. Third, the use of fundus photography instead of optical coherence tomography angiography (OCTA) is a methodological limitation, as OCTA is the gold standard for assessing retinal microvasculature. However, obtaining high-quality OCTA images is challenging in some children due to poor cooperation. Future studies are expected to employ OCTA for more comprehensive investigations to address this limitation. Fourth, significant axial length dierences between groups introduce potential myopia-related confounding, which may not be fully resolved by normalization to disc diameter. Future studies with larger, axial length-matched cohorts and advanced imaging are needed.

    Reversible cupping and persistent vessel narrowing after glaucoma surgery in childhood glaucoma: a quantitative fundus photograph study · 2026 · DOI

  • Although the precise pathogenesis is not fully understood, the current concept of glaucoma development incorporates the deformation of the lamina cribrosa caused by elevated intraocular pressure, leading to axonal damage, subsequent apoptosis of retinal ganglion cells and loss of the nerve fiber layer.

    Minimally Invasive Glaucoma Surgery: iStent and Preserflo in the Treatment of Primary Open-Angle Glaucoma. A Review · 2025 · DOI

  • Proteomic characterization of glaucoma aqueous humor (Liu et al., 2021) identified protein alterations but did not stratify findings by MMP isoforms (MMP-2, MMP-9, MMP-14) and their cognate inhibitors (TIMP-1, TIMP-2, TIMP-3, TIMP-4) across primary open-angle glaucoma subtypes.

    The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma – a literature review · 2025 · DOI

  • The differential roles of endothelin-1-mediated MMP upregulation versus endothelin receptor antagonists (e.g., Macitentan) in modulating MMP/TIMP balance during retinal ganglion cell survival have not been simultaneously measured in controlled in vivo glaucoma models.

    The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma – a literature review · 2025 · DOI

  • The segmented inner plexiform layer thickness and dendritic degeneration of retinal ganglion cells (referenced in Kim et al., 2017) have not been correlated with quantified MMP-9 and TIMP-3 expression levels in the same glaucoma patients to establish biomarker validity.

    The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma – a literature review · 2025 · DOI

  • No clinical trials have prospectively evaluated MMP inhibitors or TIMP augmentation as standalone or adjunctive therapies in chronic glaucoma patients with quantified changes in intraocular pressure, retinal nerve fiber layer thickness, and visual field progression metrics.

    The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma – a literature review · 2025 · DOI

  • The mechanistic relationship between oxidative stress-induced MMP activation and retinal ganglion cell loss in glaucoma remains incompletely characterized; studies directly measuring MMP-2 and MMP-9 substrate degradation products in cerebrospinal fluid or aqueous humor during oxidative stress in glaucoma animal models are absent.

    The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma – a literature review · 2025 · DOI

  • The review does not specify longitudinal studies tracking matrix metalloproteinase and TIMP expression changes across different stages of chronic glaucoma progression (early, moderate, advanced); comparative analysis of MMP/TIMP ratios at these specific disease stages in aqueous humor and trabecular meshwork tissue is needed.

    The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma – a literature review · 2025 · DOI

  • The measurement of the bivariate contour ellipse area, which describes fixation stability, in glaucoma gives conflicting results depending on the visual task and the measuring device.

    Why does glaucoma affect eye movements? · 2025 · DOI

  • The interventions vary widely in terms of educational content and in strategies and do not seem to follow the strategies used to educate patients with other chronic diseases.

    Improving adherence in glaucoma patients: a systematic review of patient education methods · 2011 · DOI

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38 open questions have been extracted from the limitations and future-work passages of 388 Glaucoma and retinal disorders papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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