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    Research Update 570


    Associations Between HbA1c Across the Normal Range, Diagnosed, and Undiagnosed Diabetes and Retinal Layer Thickness in UK Biobank Cohort.

    Translational vision science &  technolonogy. 2023 Feb 1;

    Chua SYL, Welsh P, Sun Z, Balaskas K, Warwick A, Steel D, Sivaprasad S, Channa R, Ko T, Sattar N, Khawaja AP, Foster PJ, Patel PJ;

    Purpose: The purpose of this study was to investigate the association between glycated hemoglobin (HbA1c) levels and retinal sub-layer thicknesses in people with and without diabetes.

    Methods: We included 41,453 UK Biobank participants aged 40 to 69 years old. Diabetes status was defined by self-report of diagnosis or use of insulin. Participants were categorized into groups: (1) those with HbA1c <48 mmol/mol were subdivided into quintiles according to normal range of HbA1c; (2) those previously diagnosed with diabetes with no evidence of diabetic retinopathy; and (3) undiagnosed diabetes: >48 mmol/mol. Total macular and retinal sub-layer thicknesses were derived from spectral-domain optical coherence tomography (SD-OCT) images. Multivariable linear regression was used to evaluate the associations between diabetes status and retinal layer thickness.

    Results: Compared with participants in the second quintile of the normal HbA1c range, those in the fifth quintile had a thinner photoreceptor layer thickness (-0.33 µm, P = 0.006). Participants with diagnosed diabetes had a thinner macular retinal nerve fiber layer (mRNFL; -0.58 µm, P < 0.001), photoreceptor layer thickness (-0.94 µm, P < 0.001), and total macular thickness (-1.61 µm, P < 0.001), whereas undiagnosed diabetes participants had a reduced photoreceptor layer thickness (-1.22 µm, P = 0.009) and total macular thickness (-2.26 µm, P = 0.005). Compared to participants without diabetes, those with diabetes had a thinner mRNFL (-0.50 µm, P < 0.001), photoreceptor layer thickness (-0.77 µm, P < 0.001), and total macular thickness (-1.36 µm, P < 0.001).

    Conclusions: Participants with higher HbA1c in the normal range had marginally thinner photoreceptor thickness, whereas those with diabetes (including undiagnosed diabetes) had meaningfully thinner retinal sublayer and total macular thickness.

    Translational Relevance: We showed that early retinal neurodegeneration occurs in people whose HbA1c levels are below the current diabetes diagnostic threshold; this might impact the management of pre-diabetes individuals.

    DOI: 10.1167/tvst.12.2.25


    Successful Treatment of Severe Peripapillary Pachychoroid Syndrome with Anti VEGF Therapy.

    Retinal cases & brief reports. 2023 Jan 3

    Abraham N, Bousquet E, Santina A, Somisetty S, Romero-Morales V, Sarraf D.

    Purpose: To describe two cases of severe peripapillary pachychoroid syndrome (PPS) successfully managed with monthly intravitreal aflibercept therapy.

    Methods: Medical and imaging records were retrospectively reviewed. Patients were imaged with ultra-widefield fluorescein and indocyanine green angiography and fundus autofluorescence. Spectral-domain optical coherence tomography (SD-OCT) was performed to evaluate macular edema and choroidal thickness. OCT angiography excluded macular neovascularization.

    Results: This report summarizes 2 cases of PPS complicated by very severe bilateral macular edema. In all 4 eyes, the diffuse intraretinal and subretinal fluid remarkably improved or completely resolved after monthly intravitreal aflibercept injections with commensurate improvement of visual acuity. Multimodal imaging documented the significant improvement of fluid and the reduction in choroidal thickening in response to anti-VEGF therapy in each case.

    Conclusion: Severe cases of PPS associated with vision loss can be successfully treated with intravitreal aflibercept therapy.

    DOI: 10.1097/ICB.0000000000001405

    Baseline Diabetic Retinopathy Severity and Time to Diabetic Macular Edema Resolution with Ranibizumab Treatment: A Meta-analysis.

    Ophthalmology,Retina. 2023 Feb 10:

    Talcott KE, Valentim CCS, Hill L, Stoilov I, Singh RP.

    Objective/Purpose: Having a better understanding of how long diabetic macular edema (DME) takes to resolve in patients with diabetic retinopathy (DR) after treatment with ranibizumab, and the factors affecting this outcome, would be of benefit to physicians and patients alike. The objective of this analysis was to evaluate the time to first DME resolution and the impact of baseline DR severity on this outcome in patients treated with ranibizumab in phase 3 clinical trials.

    Design: Meta-analysis of data from the phase 3 trials, RIDE (NCT00473382) and RISE (NCT00473330), and Diabetic Retinopathy Clinical Research Network Protocols I (NCT00444600), S (NCT01489189), and T (NCT01627249).

    Participants: Patients with DME (central subfield thickness [CST] >250 μm) and DR with Diabetic Retinopathy Severity Scale (DRSS) score between 35 and 85.

    Intervention: Intravitreal injection of ranibizumab.

    Main Outcome Measures: The time to first DME resolution (defined as CST ≤250 μm) within 24 months was evaluated overall and by baseline DR severity category per the DRSS (35/43 [mild or moderate nonproliferative DR], 47-53 [moderately severe or severe nonproliferative DR], 60 (mild proliferative DR), and 61-85 [moderately severe to severe proliferative DR]).

    Results: There were 777 patients included in the meta-analysis. The overall mean (95% CI) time to first DME resolution, adjusted for baseline CST, was 6.0 (5.6-6.4) months. The mean (95% CI) time to first DME resolution was 7.1 (6.2-7.9), 5.9 (5.2-6.6), 6.0 (4.8-7.2), and 4.5 (3.5-5.5) months for the 35/43, 47 to 53, 60, and 61 to 85 baseline DRSS categories, respectively (overall P = 0.002). By month 24, the proportion of eyes with DME resolution was 74.9% (221/295), 77.5% (299/386), 69.4 (109/157), and 78.7% (148/188) for the 35/43, 47 to 53, 60, and 61 to 85 baseline DRSS categories, respectively (overall P = 0.17).

    Conclusions: This meta-analysis of data from patients treated with ranibizumab showed that DME resolution was faster in patients with more severe DR at baseline. However, by month 24, a similar proportion of patients achieved DME resolution, regardless of baseline DR severity. These findings may guide treatment decisions and inform patient expectations in clinical practice.

    DOI: 10.1016/j.oret.2023.02.003


    Pattern And Characteristics Of Drusen Subtypes In Chinese And Indian Populations In Singapore.

    Retina (Philadelphia, Pa). 2023 Feb 1;

    Takahashi K, Song Y, Cheong KX, Fenner BJ, Teo KYC, Chee ML, Li H, Tham YC, Cheung CMG, Cheng CY, Wong TY, Yanagi Y, Tan ACS.

    Purpose: To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness.

    Methods: This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited. Pachydrusen, reticular pseudodrusen, soft and hard drusen were graded on both color fundus photographs, and optical coherence tomography imaging with automated segmentation yielding and measurements of choroidal thickness.

    Results: Nine hundred and fifty-five Chinese and 381 Indians were included in the final analysis. The pattern of pachydrusen, soft drusen, hard drusen, and reticular pseudodrusen was 14.0%, 3.7%, 12.5%, and 0.2%, respectively. Mean choroidal thickness was the thickest in eyes with pachydrusen (298.3 μm; 95% confidence interval: 290.5-306.1), then eyes with hard (298.1 μm; 95% confidence interval: 290.6-305.5) and soft drusen (293.7 μm; 95% confidence interval: 281.9-305.4) and thinnest in eyes without drusen (284.6 μm; 95% confidence interval: 280.5-288.7). Systemic associations of the various drusen subtypes also differed.

    Conclusion: Patterns, characterization and choroidal thickness of drusen subtypes, and their associations provide insights into the Asian phenotypic spectrum of age-related macular degeneration and the underlying pathogenesis.

    DOI: 10.1097/IAE.0000000000003651


    The Relationship between Dietary Calcium and Age-Related Macular Degeneration.

    Nutrients. 2023 Jan 28;

    Chen YY, Chen YJ.

    Background: Mineral element supplements are widely used in the older adult population. However, little is known of their impact on the progression of age-related macular degeneration (ARMD). The aim of this study was to examine the association between dietary micronutrients and ARMD in older adults.

    Methods: We enrolled 5227 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2008) in this cross-sectional study. ARMD was evaluated using an ophthalmic digital imaging system and digital camera. Mineral element consumption was collected using a 24-hour dietary recall. The association between mineral element use and the presence of ARMD was determined by multivariable logistic regression.

    Results: After adjusting for relevant variables, dietary calcium was negatively associated with ARMD (OR: 680, 95%CI: 0.482-0.960). In contrast to dietary form, serum concentration of calcium was not associated with ARMD. Moreover, increased dietary calcium was associated with reduced ARMD (OR: 0.684, 95%CI: 0.468-1.000).

    Conclusion: A lower consumption of dietary calcium was significantly associated with a higher risk of ARMD. Further longitudinal studies are necessary to explore these findings.

    DOI: 10.3390/nu15030671


    Quantifying burden of intravitreal injections: questionnaire assessment of life impact of treatment by intravitreal injections (QUALITII).

    BMJ open ophthalmology. 2022 Dec;

    Wang R, McClard CK, Laswell S, Mahmoudzadeh R, Salabati M, Ammar M, Vannavong J, Aziz AA, Ewald A, Calvanese AVehman EB, Fried S, Windham V, Strutt A, Saroj N, Khanani AM, Eichenbaum DA, Regillo C, Wykoff CC.

    Aim: To quantify the areas of burden experienced by patients requiring repeated intravitreal injections (IVI) in the management of exudative retinal diseases.

    Methods: The validated Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections survey was administered to patients at four retina clinical practices across four US states. The primary outcome measure was Treatment Burden Score (TBS), a single score assessing overall burden.

    Results: Of 1416 (n=657 age-related macular degeneration; n=360 diabetic macular oedema/diabetic retinopathy; n=221 retinal vein occlusion; n=178 other/uncertain) patients, 55% were women with an average age of 70 years. Patients most frequently reported receiving IVI every 4-5 weeks (40%). The mean TBS was 16.1±9.2 (range 1-48; scale of 1-54), and the TBS was higher in patients with diabetic macular oedema and/or diabetic retinopathy (DMO/DR) (17.1) compared with those with age-related macular degeneration (15.5) or retinal venous occlusive (15.3) (p=0.028). Though the mean level of discomfort was quite low (1.86) (scale 0-6), 50% of patients reported experiencing side effects more than half of the visits. Patients having received fewer than 5 IVI reported higher mean anxiety levels before (p=0.026), during (p=0.050) and after (p=0.016) treatment compared with patients having received more than 50 IVI. After the procedure, 42% of patients reported restrictions from usual activities due to discomfort. Patients reported a high mean satisfaction rating of 5.46 (scale 0-6) with the care of their diseases.

    Conclusions: The mean TBS was moderate and highest among patients with DMO/DR. Patients with more total injections reported lower levels of discomfort and anxiety but higher disruption to daily life. Despite the challenges related to IVI, the overall satisfaction with treatment remained high.

    DOI: 10.1136/bmjophth-2022-001188


    Diagnostic Accuracy of the Amsler Grid Test for Detecting Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

    JAMA ophthalmology. 2023 Feb 16

    Bjerager J, Schneider M, Potapenko, van Dijk EHC, Faber C, Grauslund J, Pfau K, Huemer J, Muttuvelu DV, Rasmussen MLR, Sabaner MC, Subhi.

    Importance: Patients with nonneovascular age-related macular degeneration (AMD) are encouraged to use the Amsler grid test for self-assessment to facilitate early diagnosis. The test is widely recommended, suggesting a belief that it signals worsening AMD, warranting its use in home monitoring.

    Objective: To systematically review studies of the diagnostic test accuracy of the Amsler grid in the diagnosis of neovascular AMD and to perform diagnostic test accuracy meta-analyses.

    Data Sources: A systematic literature search was conducted in 12 databases for relevant titles from database inception until May 7, 2022. STUDY SELECTION: Studies included those with groups defined as having (1) neovascular AMD and (2) either healthy eyes or eyes with nonneovascular AMD. The index test was the Amsler grid. The reference standard was ophthalmic examination. After removal of obviously irrelevant reports, 2 authors (J.B. and M.S.) independently screened the remaining references in full text for potential eligibility. Disagreements were resolved by a third author (Y.S.).

    Data Extraction And Synthesis: Two authors (J.B. and I.P.) independently extracted all data and evaluated quality and applicability of eligible studies using the Quality Assessment of Diagnostic Accuracy Studies 2. Disagreements were resolved by a third author (Y.S.).

    Main Outcomes And Measures: Sensitivity and specificity of the Amsler grid for detecting neovascular AMD with comparators being either healthy control participants or patients with nonneovascular AMD. RESULTS: Of 523 records screened, 10 studies were included with a total of 1890 eyes (mean participant age ranging from 62 to 83 years). Sensitivity and specificity to diagnose neovascular AMD were 67% (95% CI, 51%-79%) and 99% (95% CI, 85%-100%), respectively, when comparators were healthy control participants and 71% (95% CI, 60%-80%) and 63% (95% CI, 49%-51%), respectively, when control participants were patients with nonneovascular AMD. Overall, potential sources of bias were low across studies.

    Conclusions And Relevance: Although the Amsler grid is easy and inexpensive to use for detection of metamorphopsia, its sensitivity may be at levels typically not recommended for monitoring. Coupling this lower sensitivity with only moderate specificity to identify neovascular AMD in a population at risk, these findings suggest that such patients typically should be encouraged to undergo ophthalmic examination regularly, regardless of any results of Amsler grid self-assessment.

    DOI: 10.1001/jamaophthalmol.2022.6396


    Suprachoroidal triamcinolone acetonide for the treatment of macular edema associated with retinal vein occlusion: a pilot study.

    BMC Ophthalmology. 2023 Feb 10.

    Ali BM, Azmeh AM, Alhalabi NM.

    Background: Suprachoroidal Drug Delivery has emerged in recent years as a novel promising approach, which may help address the clinical unmet needs in the management of Retinal Vein Occlusion (RVO) associated Macular Edema (ME). In this study, we aim to evaluate the feasibility in regard of the potential efficacy and safety of suprachoroidal injection of Triamcinolone Acetonide (TA) using a microinjector as a mono-treatment of ME due to RVO.

    Methods: This trial included 16 eyes of 16 patients with RVO associated ME presenting to the department of ophthalmology, Al Mouwasat university hospital, Syria. 4 mg of preserved TA was injected suprachoroidally 4 mm away from the inferotemporal limbus using a patient-customized microinjector. After injection, patients were followed after 1 week then monthly for 3 months. Primary outcome measures included the percentage of participants with best-corrected visual acuity (BCVA) gain≥15 letters and increased intraocular pressure (IOP) ≥ 20 mmHg in months 1,2, and 3, secondary measures included mean change from baseline BCVA, central subfield thickness (CST), and IOP through each of the follow-up points in addition to other measures.

    Results: After injection, BCVA gain≥15 letters occurred in 68.7, 62.5, 50, 50% of patients at week 1 and through months 1,2 and 3 respectively, the mean BCVA improved significantly by 16.4, 16, 14.4, and 11.9 letters (p-value< 0.0005) at week 1 and months 1,2 and 3 respectively. This visual gain was associated with a significant reduction of CST by 290.94 ± 181.76 (week-1) (p-value< 0.0005), 274.31 ± 184.60 (month-1) (p-value< 0.0005), 183.50 ± 165.61 (month-2) (p-value = 0.006) and 137,75 ± 156.25 μm (month-3) (p-value = 0.038). We reported one case of increased IOP ≥ 20 mmHg in the first month that decreased in the second month. The mean change of IOP readings was not statistically significant, with an increase ranging from 0.75 mmHg after the first week (p-value = 0.09) and 0.5 mmHg after 3 months (p-value = 0.72).

    Conclusion: This study suggests that suprachoroidal TA could be well tolerated and efficacious as a mono-treatment of RVO associated ME. Future clinical trials are required to confirm its longer-term safety and efficacy and to compare this efficacy with the other therapeutic options.

    DOI: 10.1186/s12886-023-02808-5