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Vongsachang H, Bleicher ID, Reshef ER, Stagner AM, Wolkow N. Wells Syndrome Presenting as Atypical Periorbital Cellulitis. Ophthalmic Plast Reconstr Surg 2022;Abstract
A 62-year-old man presented with diffuse, painless, left-sided preseptal edema, erythema, and woody induration extending to the left temple. The induration generated an orbital compartment syndrome with markedly elevated intraocular pressure necessitating lateral canthotomy and cantholysis. Although atypical for an infectious etiology, empiric broad-spectrum intravenous antibiotics were initiated with no improvement. A tissue biopsy demonstrated extensive perivascular and interstitial eosinophils with focal flame figures, and the patient was diagnosed with a severe hypersensitivity reaction or eosinophilic cellulitis (Wells syndrome). The disease process remitted rapidly upon initiation of oral prednisone. Wells syndrome is a rare inflammatory eosinophilic dermatosis, most often presenting in the limbs and trunk, with few reports of facial and periorbital involvement. This case highlights the importance of considering Wells syndrome in the differential diagnosis of atypical periorbital cellulitis that is nonresponsive to antibiotics and reviews the clinicopathologic nature of this disease.
Parekh M, Romano D, Wongvisavavit R, Coco G, Giannaccare G, Ferrari S, Rocha-de-Lossada C, Levis HJ, Semeraro F, Calvo-de-Mora MR, Scorcia V, Romano V. DMEK graft: One size does not fit all. Acta Ophthalmol 2022;Abstract
Descemet membrane endothelial keratoplasty (DMEK) is a popular procedure for the treatment of corneal endothelial diseases mainly targeting Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). Although DMEK has multiple advantages, it is challenging in terms of graft preparation and delivery. One of the crucial factors of DMEK graft preparation is determining the size of the graft. Evaluating risks and benefits of transplanting larger or smaller grafts compared with the descemetorhexis performed following a standard DMEK procedure thus becomes important. Advanced techniques like pre-loaded DMEK requires pre-selection of graft diameter without physical examination of the eye making it more challenging. Therefore, recognizing the benefits of graft size and the number of transplanted endothelial cells becomes essential. Smaller DMEK grafts have been preferred and accepted for grafting. Larger diameter grafts have advantages but can be challenging due to higher detachment rates. We thus aim to review the challenges of preparing and delivering DMEK tissues with small or large diameter based on selected descemetorhexis area, discuss the outcomes based on different graft sizes, highlight related complications and suggest which cases may benefit from adopting smaller or larger graft size.
Agrawal R, Ludi Z, Betzler BK, Testi I, Mahajan S, Rousellot A, Kempen JH, Smith JR, McCluskey P, Nguyen QD, Pavesio C, Gupta V. The Collaborative Ocular Tuberculosis Study (COTS) calculator-a consensus-based decision tool for initiating antitubercular therapy in ocular tuberculosis. Eye (Lond) 2022;Abstract
OBJECTIVE: To introduce the Collaborative Ocular Tuberculosis Study (COTS) Calculator, an online clinical scoring system for initiating antitubercular therapy (ATT) in patients with ocular tuberculosis (TB). METHOD: The COTS Calculator was derived from COTS Consensus (COTS CON) data, which has previously published consensus guidelines. Using a two-step Delphi method, 81 experts evaluated 486 clinical scenario-based questions, ranking their likelihood of initiating ATT in each specific scenario. Each scenario was a permutation of the results and/or availability of five following components-clinical phenotype, endemicity, two immunological (tuberculin skin test, interferon-γ release assay) and one radiological (chest X-Ray) test results-and a sixth component further stratifying three of the clinical phenotypes. The median scores and interquartile ranges (IQR) of each scenario were tabulated, representing the expert consensus on whether to initiate ATT in that scenario. The consensus table was encoded to develop the COTS Calculator. RESULTS: The COTS Calculator can be accessed online at: https://www.oculartb.net/cots-calc . The attending physician can select the conditions present in the patient, which will generate a median score from 1 to 5. 114 out of 486 scenarios (24%) deliberated had a median score of 5 indicating expert consensus to initiate ATT. CONCLUSION: The COTS Calculator is an efficient, low-cost, evidence and experience-based clinical tool to guide ATT initiation. While it holds substantial promise in improving standard-of-care for ocular-TB patients, future validation studies can help to as certain its clinical utility and reliability.
Bian Y, Ma KK, Hall NE, Alice Lorch TE, Miller JW, Dana R, Yin J. Neurotrophic Keratopathy in the United States: an IRIS® Registry (Intelligent Research in Sight) Analysis. Ophthalmology 2022;Abstract
PURPOSE: To describe the characteristics of neurotrophic keratopathy (NK) in the US. DESIGN: Retrospective database study. SUBJECTS: 31,915 eyes from 27,483 patients with a diagnosis of NK. METHODS: Retrospective analysis of visits associated with a diagnosis of NK between 2013 and 2018 using the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight). MAIN OUTCOME MEASURES: Demographic information, prevalence, visual acuity (VA), concomitant diagnosis and procedure codes, risk factors impacting visual acuity closest after NK onset date. RESULTS: Mean age at initial diagnosis of NK was 68.0 (SD=16.0) years. 58.91% of patients were female (p<0.0001). Presentation was unilateral in 58.14%, bilateral in 16.13%, and unspecified in 25.73%. Average 6-year prevalence of NK in the IRIS Registry was 21.34 cases per 100,000 patients. Mean logMAR VA was 0.60 (SD=0.79) prior to diagnosis, and 0.88 (SD=0.94) after diagnosis (p<0.0001). Most common concomitant diagnoses included herpetic keratitis (33.70%), diabetes (31.59%), and corneal dystrophy (14.28%). Common procedures for NK management included the use of amniotic membrane (29.90%), punctal plugs (29.65%), and bandage contact lenses (22.67%). Age, male sex, Black race, Hispanic or Latino ethnicity, unilateral involvement, concomitant diagnoses of diabetes, corneal transplant, or herpetic keratitis were significantly associated with worse VA. CONCLUSION: Based on the IRIS Registry, the prevalence of NK is 21.34 cases per 100,000 patients. VA was significantly worse after NK diagnosis compared to other time points. NK was most commonly associated with herpetic keratitis and diabetes. Worse VA in NK patients was associated with several demographic characteristics, history of diabetes, corneal transplant, and herpetic keratitis.
Christen WG, Cook NR, Manson JAE, Buring JE, Lee I-M, Bubes V, Friedenberg G, Dushkes R, Smith D, Schaumberg DA, Schaumberg DA. Efficacy of Marine ω-3 Fatty Acid Supplementation vs Placebo in Reducing Incidence of Dry Eye Disease in Healthy US Adults: A Randomized Clinical Trial. JAMA Ophthalmol 2022;140(7):707-714.Abstract
Importance: Results of several small randomized clinical trials have suggested that supplements of marine ω-3 fatty acids may be beneficial in treating signs and symptoms of dry eye disease (DED). However, randomized clinical trial data to examine whether ω-3 fatty acid supplements can prevent DED are lacking. Objective: To evaluate whether long-term daily supplementation with marine ω-3 fatty acids prevents the development of DED. Design, Setting, and Participants: This was a prespecified ancillary study of the Vitamin D and Omega-3 Trial (VITAL), a nationwide randomized double-blind placebo-controlled 2 × 2 factorial trial of vitamin D and marine ω-3 fatty acids in the primary prevention of cancer and cardiovascular disease. Participants in this ancillary study were 23 523 US adults (men 50 years and older and women 55 years and older) who at study entry were free of a previous diagnosis of DED and were not experiencing severe dry eye symptoms. Participants were enrolled from November 2011 to March 2014, and treatment and follow-up ended on December 31, 2017. Data were analyzed from January 2020 to August 2021. Interventions: Marine ω-3 fatty acids, 1 g per day. Main Outcomes and Measures: The primary end point was incident clinically diagnosed DED confirmed by review of the medical records. The secondary end point was a composite of all confirmed incident clinically diagnosed DED cases plus all incident reports of severe DED symptoms. Results: The mean (SD) age of the 23 523 participants included in the analysis was 67.0 (7.0) years, and 11 349 participants (48.3%) were women. The cohort included 4610 participants (20.0%) who self-identified as Black, 16 481 (71.6%) who self-identified as non-Hispanic White, and 1927 (8.4%) of other racial or ethnic groups or who declined to respond, consolidated owing to small numbers, including American Indian or Alaska Native, Asian, Hispanic or Latino, and Native Hawaiian or Other Pacific Islander. During a median (range) 5.3 (3.8-6.1) years of treatment and follow-up, 472 of 23 523 participants (2.0%) experienced a medical record-confirmed diagnosis of DED. There was no difference in diagnosed DED by randomized ω-3 fatty acid assignment (232 of 11 757 participants [2.0%] with end points in the treated group vs 240 of 11 766 [2.0%] with end points in the placebo group; hazard ratio, 0.97; 95% CI, 0.81-1.16). Similarly, there was no difference between groups for the secondary end point of diagnosed DED plus incident severe DED symptoms (1044 participants [8.9%] with end points in the treated group vs 1074 [9.1%] with end points in the placebo group; hazard ratio, 0.97; 95% CI, 0.89-1.06). Conclusions and Relevance: In this randomized clinical trial, long-term supplementation with 1 g per day of marine ω-3 fatty acids for a median (range) of 5.3 (3.8-6.1) years did not reduce the incidence of diagnosed DED or a combined end point of diagnosed DED or incident severe DED symptoms. These results do not support recommending marine ω-3 fatty acid supplementation to reduce the incidence of DED. Trial Registration: ClinicalTrials.gov Identifier: NCT01880463.
Garg I, Uwakwe C, Le R, Lu ES, Cui Y, Wai KM, Katz R, Zhu Y, Moon JY, Li CY, Laíns I, Eliott D, Elze T, Kim LA, Wu DM, Miller JW, Husain D, Vavvas DG, Miller JB. Nonperfusion Area and Other Vascular Metrics by Wider Field Swept-Source OCT Angiography as Biomarkers of Diabetic Retinopathy Severity. Ophthalmol Sci 2022;2(2)Abstract
Purpose: To study the wider field swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, especially non-perfusion area (NPA), in the diagnosing and staging of DR. Design: Cross-sectional observational study (November 2018-September 2020). Participants: 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients). Methods: We imaged using 6mm×6mm and 12mm×12mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operator characteristic analysis was used for statistical analyses. Main Outcome Measures: Quantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading. Results: Among patients with diabetes (median age 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had non-proliferative DR (NPDR); and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. NPA was the best parameter to diagnose DR (AUC:0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC:0.97) and differentiated between DR stages (AUC range:0.83-0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas an increased VD and VSD in SCP among moderate-severe NPDR group. Conclusions: Our work highlights the importance of NPA, which can be more readily and easily measured with WF SS-OCTA compared to fluorescein angiography. It is additionally quick and non-invasive, and hence can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6mm×6mm and 12mm×12mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.
Zeng R, Garg I, Bannai D, Kasetty M, Katz R, Park J, Lizano P, Miller JB. Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography. Graefes Arch Clin Exp Ophthalmol 2022;Abstract
PURPOSE: To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA). METHODS: Patients with and without a diagnosis of HTN were included in this cross-sectional observational study. All eyes were imaged with SD-OCTA using 3 mm × 3 mm and 6 mm × 6 mm centered on both the fovea and optic disk. A second 6 mm × 6 mm scan was taken after a 30 s breath-hold. Vessel density (VD), vessel skeletonized density (VSD), and fractal dimension (FD) were calculated using customized MATLAB scripts. Vessel diameter index (VDI) was obtained by taking the ratio of VD to VSD. Vasoreactivity was measured by subtracting the VD or VSD before and after breath-hold (∆VD, ∆VSD). RESULTS: Twenty-three eyes with HTN (17 patients) and 17 control eyes (15 patients) were included. In the 6 mm × 6 mm angiogram centered on fovea, the superficial capillary plexus (SCP) VD (ß =  - 0.029, p = 0.012), VSD (ß =  - 0.004, p = 0.043) and the choriocapillaris VD (ß =  - 0.021, p = 0.030) were significantly decreased in HTN compared to control eyes. Similarly, FD was decreased in both the SCP (ß =  - 0.012, p = 0.013) and choriocapillaris (ß =  - 0.009, p = 0.030). In the 3 mm × 3 mm angiogram centered on optic disk, SCP VDI (ß =  - 0.364, p = 0.034) was decreased. ∆VD and ∆VSD were both reduced in the DCP (ß =  - 0.034, p = 0.032; ß =  - 0.013, p = 0.043) and ∆VSD was elevated in the choriocapillaris of HTN eyes (ß = 0.004, p = 0.032). CONCLUSIONS: The study used SD-OCTA to show significant differences in the retinal vasculature of hypertensive patients. It was also the first to demonstrate the potential of OCT-A to investigate retinal vascular reactivity in patients with HTN.
Stuart KV, Madjedi K, Luben RN, Chua SYL, Warwick AN, Chia M, Pasquale LR, Wiggs JL, Kang JH, Hysi PG, Tran JH, Foster PJ, Khawaja AP, for Collaboration MRFG. Alcohol, Intraocular Pressure, and Open-Angle Glaucoma: A Systematic Review and Meta-analysis. Ophthalmology 2022;129(6):637-652.Abstract
TOPIC: This systematic review and meta-analysis summarizes the existing evidence for the association of alcohol use with intraocular pressure (IOP) and open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding and quantifying these associations may aid clinical guidelines or treatment strategies and shed light on disease pathogenesis. The role of alcohol, a modifiable factor, in determining IOP and OAG risk also may be of interest from an individual or public health perspective. METHODS: The study protocol was preregistered in the Open Science Framework Registries (https://osf.io/z7yeg). Eligible articles (as of May 14, 2021) from 3 databases (PubMed, Embase, Scopus) were independently screened and quality assessed by 2 reviewers. All case-control, cross-sectional, and cohort studies reporting a quantitative effect estimate and 95% confidence interval (CI) for the association between alcohol use and either IOP or OAG were included. The evidence for the associations with both IOP and OAG was qualitatively summarized. Effect estimates for the association with OAG were pooled using random effects meta-analysis. Studies not meeting formal inclusion criteria for systematic review, but with pertinent results, were also appraised and discussed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: Thirty-four studies were included in the systematic review. Evidence from 10 studies reporting an association with IOP suggests that habitual alcohol use is associated with higher IOP and prevalence of ocular hypertension (IOP > 21 mmHg), although absolute effect sizes were small. Eleven of 26 studies, comprising 173 058 participants, that tested for an association with OAG met inclusion criteria for meta-analysis. Pooled effect estimates indicated a positive association between any use of alcohol and OAG (1.18; 95% confidence interval [CI], 1.02-1.36; P = 0.03; I2 = 40.5%), with similar estimates for both prevalent and incident OAG. The overall GRADE certainty of evidence was very low. CONCLUSIONS: Although this meta-analysis suggests a harmful association between alcohol use and OAG, our results should be interpreted cautiously given the weakness and heterogeneity of the underlying evidence base, the small absolute effect size, and the borderline statistical significance. Nonetheless, these findings may be clinically relevant, and future research should focus on improving the quality of evidence.
Wang F, Liu LQ, Liang RB, Zhang LJ, Shu HY, Liao XL, Pan YC, Wu J, Su T, Shao Y. Decreased Macular Retinal Thickness in Patients With Pterygium. Front Neurol 2022;13:881190.Abstract
Purpose: To explore alterations in macular retinal thickness (RT) and analyze correlation between macular RT and pterygium area, length in pterygium patients. Methods: Totally 13 patients with pterygium (left eye) and 13 healthy controls (left eye) were recruited. OCTA was applied to scan each eye to generate three-dimensional images. Based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method, each image was divided into nine subregions for the ETDRS: central (C); inner superior (IS); outer superior (OS); inner nasal (IN); outer nasal (ON); inner inferior (II); outer inferior (OI); inner temporal (IT); and outer temporal (OT). The macular RT in each subregion was measured. Furthermore, the correlation between RT and the area, length of pterygium was analyzed. Results: The visual acuity of pterygium patient was different from that of the control (P < 0.05). Besides, decreased intraretinal thickness of the IN and ON, increased intraretinal thickness of OT, decreased extraretinal thickness of OT, IN, ON, OS, and decreased retinal full layer thickness of medial superior, OS, IN, ON, and II subregions in pterygium group were observed. There was a negative correlation between RT of the IN and ON subregions and the length of pterygium (r = -0.5803 and r = -0.6013, P = 0.0376 and P = 0.0297). The RT of IN subregion was negatively correlated with pterygium area (r = -0.5844, P = 0.0359). According to the receiver operating characteristic analysis, in the ON subregion, the areas under the curve of the inner retinal thickness, outer retinal thickness and the whole retinal thickness were 1.0 (95% CI: 1.0), 0.882 (95% CI: 0.715 and 0.963), and 1.0 (95% CI: 1.0). The smallest area under the curve of retinal thickness in OT subregion was 0.018 (95% CI: 0-0.059). Conclusion: RT of pterygium patients was significantly decreased, and the main alterations occurred in the temporal side suggesting there might exist retinal structural alterations in pterygium.
Sekimitsu S, Wang J, Elze T, Segrè AV, Wiggs JL, Zebardast N. Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank. PLoS One 2022;17(6):e0270530.Abstract
BACKGROUND/AIMS: Psychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure. METHODS: This analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method. RESULTS: Among the 441,054 participants, 959 (0.22%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24±1.03 SD vs. 0.00±1.00 SD, p<0.001) and PACG prevalence increased with each decile of higher PRS. Among individuals using psychotropic medication, those with PACG had higher average PRS (0.31±1.00 SD vs. 0.00±1.00 SD, p<0.001) and were more likely to have a PRS in upper deciles of polygenic risk (p = 0.04). At each decile of PRS, psychotropic medication use was associated with increased risk of PACG. These effects were more pronounced and significant in higher deciles. CONCLUSION: We demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum.
Aleman TS, Huckfeldt RM, Serrano LW, Pearson DJ, Vergilio GK, McCague S, Marshall KA, Ashtari M, Doan TM, Weigel-DiFranco CA, Biron BS, Wen X-H, Chung DC, Liu E, Ferenchak K, Morgan JIW, Pierce EA, Eliott D, Bennett J, Comander J, Maguire AM. AAV2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial. Ophthalmology 2022;Abstract
PURPOSE: To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human CHM-encoding cDNA in choroideremia (CHM). DESIGN: Prospective, open-label, non-randomized, dose-escalation, phase 1/2 clinical trial. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Fifteen CHM patients (ages 20-57 years at dosing). METHODS, INTERVENTION, OR TESTING: Patients received uniocular subfoveal injections of low dose (up to 5x1010 vector genome (vg) per eye, n=5) or high dose (up to 1x1011 vg per eye, n=10) AAV2-hCHM. Patients were evaluated pre- and post-operatively for two years with ophthalmic examinations, multimodal retinal imaging and psychophysical testing. MAIN OUTCOME: Measures: visual acuity (VA), perimetry (10-2 protocol), spectral-domain optical coherence tomography (SD-OCT) and short-wavelength fundus autofluorescence (SW-FAF). RESULTS: We detected no vector-related or systemic toxicities. VA returned to within 15 letters of baseline in all but two patients (one developed acute foveal thinning, another patient, a macular hole); the rest showed no gross changes in foveal structure at two years. There were no significant differences between intervention and control eyes in mean light-adapted sensitivity by perimetry, or in the lateral extent of retinal pigment epithelium (RPE) relative preservation by SD-OCT and SW-FAF. Microperimetry showed non-significant (<3SD of the intervisit variability) gains in sensitivity in some locations and participants in the intervention eye. There were no obvious dose-dependent relationships. CONCLUSIONS: VA was within 15 letters of baseline after the subfoveal AAV2-hCHM injections in 13/15 (87%) of the patients. Acute foveal thinning with unchanged perifoveal function in one patient and macular hole in a second suggests foveal vulnerability to the subretinal injections. Longer observation intervals will help establish the significance of the minor differences in sensitivities and rate of disease progression observed between intervention and control eyes.
Kitazawa K, Inotmata T, Shih K, Hughes J-WB, Bozza N, Tomioka Y, Numa K, Yokoi N, Campisi J, Dana R, Sotozono C. Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis. Ocul Surf 2022;25:108-118.Abstract
PURPOSE: Dry eye disease (DED) is a common age-related ocular surface disease. However, it is unknown how aging influences the ocular surface microenvironment. This systematic review aims to investigate how the aging process changes the ocular surface microenvironment and impacts the development of DED. METHODS: An article search was performed in PubMed, EMBASE, and Web of Science. 44 studies reporting on age-related ocular changes and 14 large epidemiological studies involving the prevalence of DED were identified. 8 out of 14 epidemiological studies were further analyzed with meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (impact of aging on the prevalence of DED) were combined using one-group meta-analysis in a random-effects model. RESULTS: Meta-analysis revealed the prevalence of DED in the elderly aged 60 years old or older was 5519 of 60107 (9.2%) and the odds ratio of aging compared to younger age was 1.313 (95% confidence interval [CI]; 1.107, 1.557). With increasing age, the integrity of the ocular surface and tear film stability decreased. Various inflammatory cells, including senescent-associated T-cells, infiltrated the ocular surface epithelium, lacrimal gland, and meibomian gland, accompanied by senescence-related changes, including accumulation of 8-OHdG and lipofuscin-like inclusions, increased expression of p53 and apoptosis-related genes, and decreased Ki67 positive cells. CONCLUSIONS: The aging process greatly impacts the ocular surface microenvironment, consequently leading to DED.
Madjedi KM, Stuart KV, Chua SYL, Foster PJ, Strouthidis NG, Luben RN, Warwick AN, Kang JH, Wiggs JL, Pasquale LR, Khawaja AP. The association of female reproductive factors with glaucoma and related traits: A systematic review. Ophthalmol Glaucoma 2022;Abstract
TOPIC: This systematic review summarizes the existing evidence for the association between female reproductive factors (age at menarche, parity, oral contraceptive (OC) use, age at menopause, and postmenopausal hormone (PMH) use) and intraocular pressure (IOP) or open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding the association between female reproductive factors and glaucoma may shed light on disease pathogenesis and aid clinical prediction and personalized treatment strategies. Importantly, some factors are modifiable which may lead to new therapies. METHODS: Two reviewers independently extracted articles in Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases to identify relevant studies. Eligibility criteria included studies with human subjects over 18 years of age; a measured exposure of at least one of the following: age at menarche, parity, OC use, age at menopause, PMH use; a measured outcome of either IOP or OAG; a cohort, case-control, cross-sectional or randomized-controlled trial design; and a reported measure of association including hazard, risk or odds ratio or mean difference with associated confidence intervals. RESULTS: We included a total of 27 studies. Substantial differences in study design, exposure and treatment levels, treatment duration and variable reporting precluded meaningful quantitative synthesis of the identified studies. Overall, relatively consistent associations between PMH use and lower IOP were identified. With respect to OAG, estrogen-only PMH use may be associated with lower OAG risk and this association may be modified by race. No significant associations were found with combined estrogen + progesterone PMH use. No strong associations between parity, or age at menarche and glaucoma were found, but a younger age at menopause was associated with increased glaucoma risk, and adverse associations were identified with longer duration of OC use, though no overall association with OC use was found. CONCLUSION: The association between PMH use and lower IOP/OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies. There is a need for future research examining associations with IOP specifically, and how the relationship between genetic factors and OAG risk may be influenced by female reproductive factors.

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