American Society of Retina Specialists Clinical Practice Guidelines on Multimodal Imaging for Retinal Disease.

Purpose: Advancements in retinal imaging have augmented our understanding of the pathology and structure-function relationships of retinal disease. No single diagnostic test is sufficient; rather, diagnostic and management strategies increasingly involve the synthesis of multiple imaging modalities. Methods: This literature review and editorial offer practical clinical guidelines for how the retina specialist can use multimodal imaging to manage retinal conditions. Results: Various imaging modalities offer information on different aspects of retinal structure and function. For example, optical coherence tomography (OCT) and B-scan ultrasonography can provide insights into the microstructural anatomy; fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT angiography (OCTA) can reveal vascular integrity and perfusion status; and near-infrared reflectance and fundus autofluorescence (FAF) can characterize molecular components within tissues. Managing retinal vascular diseases often includes fundus photography, OCT, OCTA, and FA to evaluate for macular edema, retinal ischemia, and the secondary complications of neovascularization (NV). OCT and FAF play a key role in diagnosing and treating maculopathies. FA, OCTA, and ICGA can help identify macular NV, posterior uveitis, and choroidal venous insufficiency, which guides treatment strategies. Finally, OCT and B-scan ultrasonography can help with preoperative planning and prognostication in vitreoretinal surgical conditions. Conclusions: Today, the retina specialist has access to numerous retinal imaging modalities that can augment the clinical examination to help diagnose and manage retinal conditions. Understanding the capabilities and limitations of each modality is critical to maximizing its clinical utility.

Anomaly-guided weakly supervised lesion segmentation on retinal OCT images.

The availability of big data can transform the studies in biomedical research to generate greater scientific insights if expert labeling is available to facilitate supervised learning. However, data annotation can be labor-intensive and cost-prohibitive if pixel-level precision is required. Weakly supervised semantic segmentation (WSSS) with image-level labeling has emerged as a promising solution in medical imaging. However, most existing WSSS methods in the medical domain are designed for single-class segmentation per image, overlooking the complexities arising from the co-existence of multiple classes in a single image. Additionally, the multi-class WSSS methods from the natural image domain cannot produce comparable accuracy for medical images, given the challenge of substantial variation in lesion scales and occurrences. To address this issue, we propose a novel anomaly-guided mechanism (AGM) for multi-class segmentation in a single image on retinal optical coherence tomography (OCT) using only image-level labels. AGM leverages the anomaly detection and self-attention approach to integrate weak abnormal signals with global contextual information into the training process. Furthermore, we include an iterative refinement stage to guide the model to focus more on the potential lesions while suppressing less relevant regions. We validate the performance of our model with two public datasets and one challenging private dataset. Experimental results show that our approach achieves a new state-of-the-art performance in WSSS for lesion segmentation on OCT images.

Outcome of silicone sling frontalis suspension in children with simple congenital and complex ptosis.

OBJECTIVE: To compare the outcome of silicone sling frontalis suspension (FS) surgery in children with simple congenital ptosis and children with complex ptosis. DESIGN: A retrospective cohort study. PARTICIPANTS: All pediatric patients who underwent silicone sling FS surgery between 2009 and 2020 at a single centre. METHODS: Patients were divided based on etiology into simple congenital ptosis and complex congenital ptosis. Pre- and postoperative margin-to-reflex distance (MRD1) measurements were determined from clinical photographs. Main outcome measures were assessed as differences in improvement in eyelid height and reoperation rate between the groups. RESULTS: Two-hundred and eight children were included: 139 simple and 69 complex cases, with 83 females (40%). Mean (±SD) age at intervention was 1.9 ± 2.9 years. Complex cases included blepharophimosis epicanthus inversus syndrome (n = 35), Marcus Gunn jaw-winking syndrome (n = 12), oculomotor palsy (n = 8), congenital fibrosis of extraocular muscles (n = 3), chronic progressive external ophthalmoplegia (n = 3), and others. Mean MRD1 improved by an average of 1.6 mm in both groups. Repeat ptosis correction was performed in 50 of 171 patients (29%) without a history of failed ptosis procedures, and this rate was similar between simple and complex cases. Children under 3 years of age had higher rates of repeat ptosis repair than older children (n = 59 of 175 [34%] vs n = 5 of 33 [15%]; p = 0.03, χ2 test). CONCLUSIONS: Silicone sling FS has a favourable outcome in 70% of pediatric patients. Preoperative and final MRD1 and reoperation rates were similar between both groups, suggesting that despite the higher complexity in atypical cases, the outcome is similar.

Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration.

During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [- 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [- 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.

Validation of an Automated Symptom-Based Triage Tool in Ophthalmology.

OBJECTIVES: Acute care ophthalmic clinics often suffer from inefficient triage, leading to suboptimal patient access and resource utilization. This study reports the preliminary results of a novel, symptom-based, patient-directed, online triage tool developed to address the most common acute ophthalmic diagnoses and associated presenting symptoms. METHODS: A retrospective chart review of patients who presented to a tertiary academic medical center's urgent eye clinic after being referred for an urgent, semi-urgent, or nonurgent visit by the ophthalmic triage tool between January 1, 2021 and January 1, 2022 was performed. Concordance between triage category and severity of diagnosis on the subsequent clinic visit was assessed. RESULTS: The online triage tool was utilized 1,370 and 95 times, by the call center administrators (phone triage group) and patients directly (web triage group), respectively. Of all patients triaged with the tool, 8.50% were deemed urgent, 59.2% semi-urgent, and 32.3% nonurgent. At the subsequent clinic visit, the history of present illness had significant agreement with symptoms reported to the triage tool (99.3% agreement, weighted kappa = 0.980, p < 0.001). The triage algorithm also had significant agreement with the severity of the physician diagnosis (97.0% agreement, weighted kappa = 0.912, p < 0.001). Zero patients were found to have a diagnosis on exam that should have corresponded to a higher urgency level on the triage tool. CONCLUSION: The automated ophthalmic triage algorithm was able to safely and effectively triage patients based on symptoms. Future work should focus on the utility of this tool to reduce nonurgent patient load in urgent clinical settings and to improve access for patients who require urgent medical care.

Current Concepts of the Uveitis-Glaucoma-Hyphema (UGH) Syndrome.

PURPOSE: To discuss the pathophysiology, etiology, and current management strategies of uveitis-glaucoma-hyphema (UGH) syndrome. METHODS: Literature review. RESULTS: The classic UGH syndrome associated with anterior chamber intraocular lenses (ACIOL) have decreased in incidence with the modernization of IOL design and surgical techniques. The current UGH syndrome is increasing in prevalence largely related to a parallel increase in late onset dislocations of intraocular lenses (IOLs) and the developing techniques to remedy that condition. The modern features of UGH can present as cystoid macular edema, intraocular pressure elevation typically not attributed to UGH, and recurrent vitreous hemorrhage, unlike the original description as described by Ellingson in 1978. Medical management to control inflammation, reduce intraocular pressure, and reduced the bleeding diathesis are mainstays of therapy. However, surgery with IOL repositioning or exchange should be reserved for cases that are refractory to or progressing despite medical treatment. CONCLUSIONS: UGH syndrome is an increasingly common, poorly understood, and often subtle, manifestation of an anatomic disturbance post intraocular surgery that persists with continued evolution of intraocular surgical techniques and new imaging modalities to aid in its diagnosis.

Evolution of the 'omega sign' on optical coherence tomography.

PURPOSE: To present the early post-operative evolution of retained subretinal perfluoro-n-octane (PFO) as captured on OCT. METHODS: Case report of a patient. RESULTS: A 58-year-old woman was noted to have subretinal PFO after undergoing autologous retinal graft for macular hole closure under PFO tamponade. Serial OCT identified the subretinal PFO as early as the first postoperative day and demonstrates progressive consolidation and encapsulation of the PFO bubble by the surrounding outer retina. CONCLUSION: Subretinal PFO is usually seen several weeks in the postoperative course once the gas endotamponade has resorbed sufficiently for OCT imaging. In this case, PFO tamponade enabled its imaging early. Its subsequent evolution into the classic "omega sign" may suggest a granulomatous encapsulation of the PFO bubble.

Macular Vascular Imaging and Connectivity Analysis Using High-Resolution Optical Coherence Tomography.

Purpose: To characterize macular blood flow connectivity in vivo using high-resolution optical coherence tomography (HighRes OCT). Methods: Cross-sectional, observational study. Dense (6-µm interscan distance) perifoveal HighRes OCT raster scans were performed on healthy participants. To mitigate the limitations of projection-resolved OCT-angiography, flow and structural data were used to observe the vascular structures of the superficial vascular complex (SVC) and the deep vascular complex. Vascular segmentation and rendering were performed using Imaris 9.5 software. Inflow and outflow patterns were classified according to vascular diameter and branching order from superficial arteries and veins, respectively. Results: Eight eyes from eight participants were included in this analysis, from which 422 inflow and 459 outflow connections were characterized. Arteries had direct arteriolar connections to the SVC (78%) and to the intermediate capillary plexus (ICP, 22%). Deep capillary plexus (DCP) inflow derived from small-diameter vessels succeeding ICP arterioles. The most prevalent outflow pathways coursed through superficial draining venules (74%). DCP draining venules ordinarily merged with ICP draining venules and drained independently of superficial venules in 21% of cases. The morphology of DCP draining venules in structural HighRes OCT is distinct from other vessels crossing the inner nuclear layer and can be used to identify superficial veins. Conclusions: Vascular connectivity analysis supports a hybrid circuitry of blood flow within the human parafoveal macula. Translational Relevance: Characterization of parafoveal macular blood flow connectivity in vivo using a precise segmentation of HighRes OCT is consistent with ground-truth microscopy studies and shows a hybrid circuitry.

Silicone sling frontalis suspension for congenital ptosis: Outcome of 174 consecutive cases.

BACKGROUND: Frontalis suspension (FS) is the treatment of choice in congenital ptosis with poor levator function. We report the surgical outcome of FS using a double triangle configuration of silicone slings in children. METHODS: A retrospective cohort study of all paediatric patients with simple myogenic congenital ptosis repaired with FS over a 12-year period (2009-2020). Each silicone sling was secured by simple knots. Pre- and post-operative margin reflex distance (MRD1 ) measurements were determined from clinical photographs using ImageJ Software. Main outcome measures were improvement in eyelid height, eyelid asymmetry, reoperation rate and timing. RESULTS: One hundred and thirty nine patients (174 eyes) were included, with 35 (25%) having bilateral surgery. Mean (±SD) age was 1.4 ± 1.9 years. Mean follow up time was 32 ± 20.5 months. Sixteen patients (11%) had a history of previous ptosis repair surgery. Mean MRD1 improved by an average of 1.5 mm. The final MRD1 in the group of patients who did not have a second procedure was a mean of 2.1 mm. The MRD1 difference between both eyes in all unilateral cases improved from 2.5 mm preoperatively to 1.2 mm at final visit (p < 0.001). In the 123 cases without a history of previous ptosis surgery, repeat ptosis repair was performed in 37 (30%) patients, 34.9 ± 19.9 months after the initial procedure. Overall, repeat repair was performed in 47 patients (34%). CONCLUSIONS: Double triangle silicone sling frontalis suspension has a favourable outcome in two-thirds of paediatric patients with simple myogenic congenital ptosis. Failed cases can be addressed with a second repair, using either autogenous fascia lata or a second silicone sling.

Telemedicine in neuro-ophthalmology.

PURPOSE OF REVIEW: The COVID-19 public health emergency accelerated the adoption of telemedicine in neuro-ophthalmology. This review surveys the current telemedicine landscape and discusses associated limitations and opportunities. RECENT FINDINGS: Logistic considerations and regulatory changes related to the COVID-19 pandemic have spurred a proliferation of tele-neuro-ophthalmic practice. One significant benefit of telemedicine is increased access to the limited number of neuro-ophthalmologists in the country. Certain elements of the neuro-ophthalmic examination can be ascertained during a video visit or through the use of mobile applications. However, data quality can be limited and more direct evaluation of the fundus currently requires the implementation of imaging techniques, such as fundus photography and/or optical coherence tomography. For cases that require it, a 'hybrid' model can be adopted in which patients physically present to designated locations for testing and subsequently participate in televisit with the physician to discuss the assessment and plan. SUMMARY: Telemedicine provides an alternate pathway for patients to access the limited resource of neuro-ophthalmic care, and it will likely persist beyond the current COVID-19 pandemic. It has some limitations currently but continued progress in technologic, legal, and reimbursement strategies will hopefully facilitate further adoption.

Visit adherence and visual acuity outcomes in patients with diabetic macular edema: a secondary analysis of DRCRnet Protocol T.

PURPOSE: To quantify the association between visit adherence and visual acuity (VA) in diabetic macular edema (DME). METHODS: This secondary analysis of the 2-year DRCRnet Protocol T study of 656 patients required one visit every 4 weeks in the first year, then at variable 4-16-week intervals in the second year. Visit adherence measured as number of missed visits, average (avg days) and longest (max days) visit interval, average (avg missed days) and longest (max missed days) unintended visit interval, and visit constancy (percentage of 3-month periods with at least 1 visit). Avg and max missed days were categorized as on time (0 days), late (> 0-60 days), and very late (> 60 days). Primary outcome was change in ETDRS VA between baseline study visit and last attended visit, using multivariate linear regression models controlling for age, gender, race, ethnicity, treatment arm, baseline VA, hemoglobin A1c, insulin use, and number of lasers and injections. RESULTS: Mean number of missed visits was 1.7. 616 (94%) patients had 100% visit constancy. A total of 331 (51%) patients were on time, 171 (26%) late, and 154 (23%) very late in avg missed days. Max missed days ranged 0-696 days. Adjusted, each missed visit was associated with 0.3-letter decrease (95%CI - 0.6, - 0.1, p = 0.02); being very late in avg and max missed days saw - 4.2 letters (95%CI - 6.4, - 2.0, p < 0.001) and - 4.0 letters (95%CI - 6.1, - 1.9, p < 0.001), respectively, than on time. Those that averaged > 4 days missed per attended visit saw 4.6 letters worse (95%CI - 7.3, - 2.0, p < 0.001). CONCLUSIONS: Visit adherence is associated with visual acuity outcomes in DME patients.

Multiple Evanescent White Dot Syndrome: Findings from a Large Northern California Cohort.

PURPOSE: To report the clinical and imaging characteristics of multiple evanescent white dot syndrome (MEWDS) from a large single-center cohort. DESIGN: Single-center, retrospective cohort study. PARTICIPANTS: A total of 111 patients previously diagnosed with MEWDS in the Kaiser Permanente Northern California system from 2012 to 2019. METHODS: Two retina specialists reviewed the medical records and all available retinal imaging, including Humphrey visual field testing, fundus photography (FP), OCT, fluorescein angiogram (FA), and fundus autofluorescence (FAF). Patients were excluded from analysis if confirmatory imaging was unavailable. MAIN OUTCOME MEASURES: Patient characteristics, visual acuity, clinical examination and imaging findings, and final diagnosis. RESULTS: Seventy-three patients (65.8%) were confirmed to have the diagnosis of MEWDS. Fifty-eight (79.5%) were female, with a mean (standard deviation [SD]) age at presentation of 35.2 (14.2) years, and mean refractive error of -1.6 diopters. Initial mean (SD) visual acuity was logarithm of the minimum angle of resolution (logMAR) 0.39 (0.31) and improved to mean (SD) logMAR 0.07 (0.15) at final follow-up. Presenting symptoms included blurred vision (82%), scotomas (56%), photopsias (43%), and floaters (23%). Nine patients (12%) had a previously diagnosed autoimmune condition, and 2 patients (3%) had documentation of a recent vaccination. Antecedent upper respiratory infection was documented in 15 of 66 patients (23%). Noted clinical and imaging features include ellipsoid zone disruption (100%), white fundus lesions (92%), FA hyperfluorescence (92%), foveal granularity (74%), vitreous cell (53%), and optic disc edema (52%). Twenty-nine of the 111 patients (26%) were initially misdiagnosed with MEWDS and subsequently given an alternative diagnosis, including other white dot syndromes, syphilis, primary vitreoretinal lymphoma, myopic degeneration, and central serous chorioretinopathy. CONCLUSIONS: Multiple evanescent white dot syndrome is a rare self-limiting condition of the outer retina. Although a distinct set of clinical exam and imaging findings permit recognition of this disease, misdiagnosis is not uncommon.

Netarsudil-associated epithelial keratopathy.

PURPOSE: To report 2 cases with a novel finding of bullous epithelial keratopathy associated with netarsudil use. OBSERVATIONS: A 72-year-old man with history of primary open angle glaucoma was started on netarsudil daily in both eyes for uncontrolled intraocular pressures despite treatment with latanoprost, brimonidine, and dorzolamide-timolol. One month later he presented with bilateral conjunctival hyperemia, predominantly inferior corneal epithelial bullae, and keratic precipitates without hypopyon. Netarsudil was discontinued, and the patient was started on topical steroids. One week later, the hyperemia and corneal edema had resolved while many small keratic precipitates persisted.A 29-year-old man with history of rubella-associated glaucoma and chronic postoperative inflammation on prednisolone was started on netarsudil in his left eye only for elevated intraocular pressures despite latanoprost, brimonidine, and dorzolamide-timolol. Two months later, he complained of eye pain and decreased vision since starting netarsudil. Examination revealed mild hyperemia and inferior corneal epithelial bullae without keratic precipitates. Netarsudil was discontinued, and two weeks later, conjunctival injection resolved and cornea cleared. CONCLUSIONS AND IMPORTANCE: Netarsudil ophthalmic solution 0.02% (Rhopressa) is a rho-kinase inhibitor recently approved for lowering intraocular pressure in open-angle glaucoma or ocular hypertension. As netarsudil continues to be increasingly used, physicians and patients need to be aware of this new possible adverse effect.

Glioblastoma multiforme mimicking optic neuritis.

PURPOSE: To present a case of glioblastoma multiforme which initially presented with only ophthalmic manifestations. OBSERVATIONS: A 48-year-old man presented with decreased vision and pain with eye movements of the right eye. MRI of the brain showed increased T2/FLAIR signal involving the right optic nerve with no other identified abnormalities. He was treated with intravenous steroids for presumed optic neuritis. His visual acuity then rapidly worsened to no light perception, with new orbital apex symptoms including central retinal artery and vein occlusions and inferior division third and fourth nerve palsies. Repeat MRI with contrast showed perineural enhancement surrounding the right optic nerve and markedly reduced diffusion along its entire course. After an unrevealing initial workup and then a 7 month period during which the patient refused follow up, he re-presented with left sided weakness, headache, and confusion. Repeat brain MRI revealed a large mass involving the right optic nerve, optic chiasm, basal ganglia, corpus callosum and brainstem. Biopsy led to a diagnosis of WHO grade IV glioblastoma multiforme. The disease was poorly responsive to temozolomide, bevacizumab and external beam radiation, and the patient passed away 5 months later. CONCLUSIONS AND IMPORTANCE: Malignant optic glioma of adulthood is a challenging diagnosis with a poor prognosis. This rare case highlights the importance of maintaining neoplasm in the differential for optic neuritis masqueraders.

Association of Visit Adherence and Visual Acuity in Patients With Neovascular Age-Related Macular Degeneration: Secondary Analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial.

Importance: Visit adherence has been shown to play a significant role in patient health outcomes. The effect of missing visits on visual acuity (VA) in individuals with neovascular age-related macular degeneration has yet to be characterized. Objective: To quantify the association between patients' adherence to randomized clinical trial visits and VA in individuals with neovascular age-related macular degeneration based on 4 visit adherence metrics. Design, Setting, and Participants: This is a secondary analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial randomized clinical trial. Individuals with age-related macular degeneration were recruited from 44 clinical centers in the United States between February 2008 and December 2009. The 2-year study protocol required 1 visit every 4 weeks (every 21-35 days for a total of 26 visits) for monthly vs pro re nata treatments of bevacizumab vs ranibizumab. Analysis took place from November 2018 through May 2019. Exposures: Visit adherence was measured in 4 ways: total number of missed visits, average number of days (avg days) between each visit, longest duration in days (max days) between visits, and visit constancy (the tally of 3-month periods with at least 1 visit attended). Average and max days were also categorized as on time (28-35 days), late (36-60 days), and very late (>60 days). Main Outcomes and Measures: Change in Early Treatment Diabetic Retinopathy Study VA between the baseline and the last visit. Linear multivariate regression models were applied to analyze the association between visit adherence and change in VA, controlling for age, sex, baseline VA, anti-vascular endothelial growth factor drug, number of injections, and dosing regimen. Results: Of 1178 patients, the mean (SD) age was 79.1 (7.3) years, and 727 (61.7%) were women. The mean (SD) number of missed visits was 2.4 (3.1). Overall, 1091 patients (92.6%) had complete visit constancy during the entire study period. Average days were categorized with 1060 patients (90.0%) classified as on time, 108 (9.2%) were late, and 10 (0.8%) were very late. For max days between visits, 197 patients (16.7%) were on time, 773 (65.6%) were late, and 208 (17.7%) were very late. After controlling for covariates, the late (avg days = -6.1; max days = -2.0) and very late (avg days = -12.5; max days = -5.9) groups saw fewer letters in both the avg and max days categories than patients in the on-time group (P < .001). Conclusions and Relevance: These results provide evidence to support the concept that visit adherence contributes to VA outcomes in neovascular age-related macular degeneration. The magnitude of the association of visit adherence with VA outcomes in this clinical scenario suggests that substantial effort should be expended to strive for visit adherence or therapeutic strategies that reduce the visit burden without compromising VA outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT00593450.

Lupus Miliaris Disseminatus Faciei of the Posterior Eyelids: A Case Report.

A 70-year-old woman with a history of Demodex blepharitis presented with a 1-year history of red-yellow nodules in the tarsus of her eyelids. Excisional biopsy revealed robust caseating granulomatous inflammation, consistent with the diagnosis of lupus miliaris disseminatus faciei. Lupus miliaris disseminatus faciei is a rare granulomatous dermatosis of unknown etiology. Estimated 200 cases have been reported to date, but none have been reported affecting the posterior lamellae of the eyelids. Lupus miliaris disseminatus faciei classically presents as symmetric yellow or brown papules on the central face and eyelid skin. Infectious etiologies and systemic granulomatous disease need to be ruled out with histologic staining and serologies.

Mitochondrial haplogroup L1c2 is associated with increased disease severity in African American patients with primary open-angle glaucoma.

OBJECTIVE: The purpose of this study is to evaluate the role mitochondrial inheritance plays in primary open-angle glaucoma (POAG) characteristics in African Americans. METHODS: POAG cases from the L1c2 and L1b mitochondrial haplogroups were compared in a retrospective case-case study. Twenty-six pairs of self-identified African American POAG cases from L1c2 and L1b mitochondrial haplogroups matched on age (mean [SD] = 71.2 [9.6] and 71.3 [9.6] years, respectively; p = 0.97), sex (21 female and 5 male pairs), and family history of glaucoma (positive in 15/26 [58%] pairs) were included. RESULTS: L1c2 subjects displayed higher vertical cup-to-disc ratio (0.75 [0.12] and 0.67 [0.16], respectively; p = 0.01, Bonferroni-corrected p = 0.08), worse pattern standard deviation on visual field (VF) testing (5.5 [3.5] and 3.5 [2.7]; p = 0.005, Bonferroni-corrected p = 0.02), and more severe glaucoma based on American Glaucoma Society staging criteria (p = 0.04, Bonferroni-corrected p = 0.32) compared to L1b subjects. L1c2 also trended towards worse mean deviation on VF compared to L1b (-8.2 [7.6] and -5.8 [6.8], respectively, p = 0.17). Best corrected visual acuity, central corneal thickness, maximum intraocular pressure (IOP), and cataract severity were comparable between L1c2 and L1b haplogroups (p ≥ 0.49), as was retinal nerve fiber layer thickness on optical coherence tomography (75.1 [14.1] and 75.1 [13.0]; p = 0.99). CONCLUSION: Results demonstrated worse glaucomatous cupping and more severe VF loss in the L1c2 compared to the L1b haplogroup despite comparable IOP. Findings implicate mitochondrial inheritance as a factor affecting POAG severity and may ultimately contribute to stratifying POAG patients into phenotypically and genotypically distinct subgroups.