Macular Disease Foundation Australia logo

    Research Update 580


    Levodopa is associated with reduced development of neovascular age-related macular degeneration.

    Ophthalmology Retina. 2023 May 3

    Hyman MJ, Skondra D, Aggarwal N, Moir J, Boucher N, McKay BS, MacCumber MW, Lavine JA.

    Objective: To determine if levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular AMD. DESIGN: Three studies were performed: Retrospective analyses in the Vestrum Health Retina Database (#1-2). Case-control analysis in the Merative™ MarketScan® Research Databases (#3).

    Participants: Eyes with neovascular AMD and 2 years of follow up (#1). Eyes with non-neovascular AMD and 1-5 years of follow up (#2). Patients aged 55 years and older with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3).

    Methods: Eyes were divided into two groups (#1-2). Exposed to L-DOPA before or on the date of neovascular (#1) or non-neovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted age, sex, AREDS status, dry AMD stage, smoking history, number of intravitreal injections at years 1 and 2 (#1), and conversion rate to neovascular AMD at years 1 – 5 (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative two-year dose in grams (g) by tertiles (<100mg, ∼100-300mg, and >∼300mg per day, #3).

    Main Outcome and Measures: Number of intravitreal injections by unpaired t-test (#1), detection of new onset neovascular AMD (#2-3) by multivariable logistic regression after adjusting for AMD risk factors.

    Results: In the Vestrum Database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N=84,088 control vs 530 L-DOPA eyes, p=0.0015). In eyes with non-neovascular AMD (N=42,081-203,155 control vs 314-1,525 L-DOPA eyes), L-DOPA exposure was associated with reduced risk of conversion to neovascular AMD by 21% at year 2 (p=0.029), 35% at years 3-4 (p<0.001), and 28% at year 5 (p=0.024). In the MarketScan Databases (N=86,900 per group), cumulative two-year doses of L-DOPA between ∼100-300mg per day and >∼300mg were associated with decreased odds of developing neovascular AMD by 14% (OR 0.86, 95% CI 0.75-0.97) and 23% (OR 0.77, 95% CI 0.67-0.87), respectively.

    Conclusions: L-DOPA use was associated with reduced detection of new onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low dose L-DOPA reduces neovascular AMD conversion.

    DOI: 10.1016/j.oret.2023.04.014


    Clinical validation for automated geographic atrophy monitoring on OCT under complement inhibitory treatment.

    Science Reports. 2023 Apr 29

    Mai J, Lachinov D, Riedl S, Reiter GS, Vogl WD, Bogunovic H, Schmidt-Erfurth U.

    Geographic atrophy (GA) represents a late stage of age-related macular degeneration, which leads to irreversible vision loss. With the first successful therapeutic approach, namely complement inhibition, huge numbers of patients will have to be monitored regularly. Given these perspectives, a strong need for automated GA segmentation has evolved. The main purpose of this study was the clinical validation of an artificial intelligence (AI)-based algorithm to segment a topographic 2D GA area on a 3D optical coherence tomography (OCT) volume, and to evaluate its potential for AI-based monitoring of GA progression under complement-targeted treatment. 100 GA patients from routine clinical care at the Medical University of Vienna for internal validation and 113 patients from the FILLY phase 2 clinical trial for external validation were included. Mean Dice Similarity Coefficient (DSC) was 0.86 ± 0.12 and 0.91 ± 0.05 for total GA area on the internal and external validation, respectively. Mean DSC for the GA growth area at month 12 on the external test set was 0.46 ± 0.16. Importantly, the automated segmentation by the algorithm corresponded to the outcome of the original FILLY trial measured manually on fundus autofluorescence. The proposed AI approach can reliably segment GA area on OCT with high accuracy. The availability of such tools represents an important step towards AI-based monitoring of GA progression under treatment on OCT for clinical management as well as regulatory trials.

    DOI: 10.1038/s41598-023-34139-2

    The correlation of retinal neurodegeneration and brain degeneration in patients with Alzheimer’s disease using optical coherence tomography angiography and MRI.

    Frontiers Aging Neuroscience. 2023 Apr 12

    Zhao B, Yan Y, Wu X, Geng Z, Wu Y, Xiao G, Wang L, Zhou S, Wei L, Wang K, Liao R.

    Introduction: Pathological changes in Alzheimer’s disease can cause retina and optic nerve degeneration. The retinal changes are correlated with cognitive function. This study aimed to explore the relationship of retinal differences with neuroimaging in patients with Alzheimer’s disease, analyze the association of cognitive function with retinal structure and vascular density, and identify potential additional biomarkers for early diagnosis of Alzheimer’s disease.

    Method: We performed magnetic resonance imaging (MRI) scans and neuropsychological assessments in 28 patients with mild Alzheimer’s disease and 28 healthy controls. Retinal structure and vascular density were evaluated by optical coherence tomography angiography (OCTA). Furthermore, we analyzed the correlation between neuroimaging and OCTA parameters in patients with mild Alzheimer’s disease with adjustment for age, gender, years of education, and hypertension.

    Results: In patients with mild Alzheimer’s disease, OCTA-detected retinal parameters were not significantly correlated with MRI-detected neuroimaging parameters after Bonferroni correction for multiple testing. Under multivariable analysis controlled for age, gender, years of education, and hypertension, the S-Hemi (0-3) sector of macular thickness was significantly associated with Mini-cog (β = 0.583, P = 0.002) with Bonferroni-corrected threshold at P < 0.003.

    Conclusion: Our findings suggested decreased macular thickness might be associated with cognitive function in mild AD patients. However, the differences in retinal parameters didn’t correspond to MRI-detected parameters in this study. Whether OCTA can be used as a new detection method mirroring MRI for evaluating the effect of neuronal degeneration in patients with mild Alzheimer’s disease still needs to be investigated by more rigorous and larger studies in the future.

    DOI: 10.3389/fnagi.2023.1089188


    Improving blood flow in occluded veins to reduce anti-vascular endothelial growth factor injections for branch retinal vein occlusion.

    American Journal of Ophthalmology Case Reports. 2023 Apr 23

    Maeno T, Aso K, Hashimoto R, Masahara H.

    Purpose: To assess the relationship between improving blood flow via arteriovenous (AV) sheathotomy without vitrectomy and the total number of anti-vascular endothelial growth factor injections (VEGF) required to treat branch retinal vein occlusion (BRVO).

    Methods: In this prospective, clinical case series, 16 eyes of 16 patients at the Toho University Sakura Medical Center with best-corrected visual acuity (BCVA) of 20/40 or worse due to macular edema associated with BRVO were analyzed for 12 months. AV sheathotomy was performed without vitrectomy for all cases. On the second day after surgery, anti-VEGF was injected into the operated eye. During the 12-month follow-up after surgery, pro re nata injections were administered when changes in foveal exudation and BCVA were evident. The blood flow of the occluded vein was assessed before and after AV sheathotomy during the operation using laser speckle flowgraphy. The total number of anti-VEGF injections, central retinal thickness (CRT), and BCVA 12 months after surgery were examined.

    Results: The changes in CRT and BCVA from baseline to month 12 were statistically significant (P < 0.01). No additional anti-VEGF injections were required for nine of 16 eyes (56.3%) during the 12 months. The total number of anti-VEGF injections for 12 months correlated with the change rate of blood flow in an occluded vein before and after AV sheathotomy (r = -2.816, P = 0.022).

    Conclusions and Importance: Improved blood flow in occluded vein may reduce the need for anti-VEGF injections in BRVO.

    DOI: 10.1016/j.ajoc.2023.101847


    Decreased Central Macular Choriocapillaris Perfusion Correlates with Increased Low Luminance Visual Acuity Deficits.

    American Journal Ophthalmology. 2023 May 2

    Shen M, Li J, Shi Y, Zhang Q, Liu Z, Zhou H, Lu J, Cheng Y, Chu Z, Zhou X, Liu J, Jiang X, Wang L, Laiginhas R, de Sisternes L, Vanner EA, Feuer WJ, Wang RK, Gregori G, Rosenfeld PJ.

    Purpose: Correlations between low luminance visual acuity deficits (LLVADs) and central choriocapillaris perfusion deficits were investigated to help explain how increases in LLVAD scores at baseline predict annual growth rates of geographic atrophy (GA).

    Design: Prospective cross-sectional study.

    Methods: Photopic luminance best-corrected visual acuity (PL-BCVA) and low luminance BCVA (LL-BCVA) were measured using the Early Treatment Diabetic Retinopathy Study chart. LL-BCVA was measured using a 2.0-log unit neutral density filter. LLVADs were calculated as the difference between PL-BCVA and LL-BCVA. Within a fovea-centered 1mm circle, the percentage of choriocapillaris flow deficits (CC FD%), drusen volume, optical attenuation coefficient (OAC) elevation volume, and the outer retinal layer (ORL) thickness were assessed.

    Results: In all 90 eyes (30 normal eyes; 31 drusen-only eyes; 29 non-foveal GA eyes), significant correlations were found between the central CC FD% and PL-BCVA (r=-0.393, p<0.001), LL-BCVA (r=-0.534, p<0.001), and the LLVAD (r=0.439, p<0.001). Central cube root (cubrt) drusen volume, cubrt OAC elevation volume, and ORL thickness were correlated with PL-BCVA, LL-BCVA and LLVADs (all p<0.05). Stepwise regression models showed that central cubrt OAC elevation volume and ORL thickness were associated with PL-BCVA (R2=0.24, p<0.05); central CC FD%, cubrt OAC elevation volume, and ORL thickness were associated with LL-BCVA (R2=0.44, p<0.01); and central CC FD% and ORL thickness were associated with LLVAD (R2=0.24, p<0.01).

    Conclusions: The significant correlations between central CC FD% and LLVAD support the hypothesis that the ability of LLVAD to predict the growth of GA is mediated through a decrease in macular choriocapillaris perfusion.

    DOI: 10.1016/j.ajo.2023.04.011


    The zeaxanthin present in a tomato line rich in this carotenoid is as bioavailable as that present in the food sources richest in this xanthophyll.

    Food Research International. 2023 Jun

    Morand-Laffargue L, Hirschberg J, Halimi C, Desmarchelier C, Borel P.

    It is strongly suspected that, like lutein, zeaxanthin (ZEA) plays a biological role in the human eye. Many studies also suggest that it could reduce the risk of age-related macular degeneration and improve cognition. Unfortunately, it is only present in a very limited number of foods. This is why a new tomato line, named “Xantomato”, whose fruits can synthesize this compound, was generated. However, whether ZEA in Xantomato is bioavailable enough for Xantomato to qualify as a nutritionally relevant ZEA source is not known. The objective was to compare the bioaccessibility and intestinal cell uptake efficiency of ZEA from Xantomato to that present in the richest sources of this compound. Bioaccessibility was assessed using in vitro digestions and uptake efficiency using Caco-2 cells. Xantomato ZEA bioaccessibility was not statistically different from that of common fruits and vegetables rich in this compound. Xantomato ZEA uptake efficiency (7.8%) was lower (P < 0.05) than that of orange pepper (10.6%) but not different from that of corn (6.9%). Therefore, the results of the in vitro digestion/Caco-2 cell model suggest that Xantomato ZEA could be as bioavailable as that found in common food sources of this compound.

    DOI: 10.1016/j.foodres.2023.112751


    Management of a unique case of Coats’-like X-linked retinitis pigmentosa associated with a RPGR variant in the era of anti-VEGF.

    Retinal cases brief reports. 2023 Mar 28.

    Pederzolli M(, Sacconi R, Bandello F, Querques G.

    Purpose: To describe a unique case of X-linked Coats-like Retinitis Pigmentosa (CLRP), a form of exudative Retinitis Pigmentosa, in association with a RPGR variant, and its management with intravitreal anti-Vascular Endothelium Growth Factor drugs (anti-VEGFs), along with a peculiar OCT finding observed in a late stage of disease.

    Methods: Case report. RESULTS: A 33-year-old man previously treated with anti-VEGFs for macular edema came to our clinic for bilateral visual loss. A hemizygous RPGR variant (c.2442_2445del) was found and a diagnosis of CLRP was made. He was initially treated with carbonic anhydrase inhibitors; when efficacy wore off, he was switched to anti-VEGF injections in both eyes with improvement. After a year without treatment, visual acuity drastically worsened in both eyes; optical coherence tomography displayed disruption and increased hyperreflectivity of the inner retinal layers in the right eye.

    Conclusion: The c.2442_2445del variant is added to the number of known ORF 15 RPGR mutations associated with CLRP. Anti-VEGF treatment was successful in blocking visual loss in our patient and withholding treatment had a negative impact on his visual outcome.

    DOI: 10.1097/ICB.0000000000001426

    Pigmentary retinopathy associated with immune therapy for advanced cutaneous melanoma.

    American Journal Ophthalmology Case Reports. 2023 Apr 18

    Lin AC, Park SJ, Daniels GA, Borooah S.

    Purpose: To describe a case of bilateral retinal pigmentary changes in the setting of immune checkpoint inhibitor therapy (ICIT).

    Observations: A 69-year-old man with a history of advanced cutaneous melanoma was started on combination ICIT with nivolumab and ipilimumab and stereotactic body radiation therapy. Soon after, he developed photopsias and nyctalopia with findings of discrete retinal pigmentary changes bilaterally. Initial visual acuities were 20/20 and 20/30 in the right and left eye, respectively. Multi-modal imaging revealed sub-retinal deposits with progressive changes in pigmentation and autofluorescence, associated with decreased peripheral fields on formal perimetry. A full-field electroretinogram revealed attenuated and delayed a- and b-waves. Positive serum retinal autoantibodies were identified. The patient developed left-sided optic nerve edema and center-involving cystoid macular edema which improved after treatment with sub-tenon’s triamcinolone.

    Conclusions: The use of ICIT has greatly expanded in oncologic practice with subsequent increases in immune related adverse events that pose significant systemic and ophthalmologic morbidities. We propose that the new retinal pigmentary changes seen in this case are the sequelae of an autoimmune inflammatory response against pigmented cells. This adds to the rare side effects that may occur after ICIT.

    DOI: 10.1016/j.ajoc.2023.101849


    Gut Microbiota Dysbiosis in Diabetic Retinopathy-Current Knowledge and Future Therapeutic Targets.

    Life (Basel, Switzerland). 2023 Apr 7;

    Serban D, Dascalu AM, Arsene AL, Tribus LC, Vancea G, Pantea Stoian A, Costea DO, Tudosie MS, Stana D, Cristea BM, Nicolae VA, Tudor C, Costea AC, Comandasu M, Faur M, Tanasescu C.

    Diabetic retinopathy is one of the major causes of blindness today, despite important achievements in diagnosis and therapy. The involvement of a gut-retina axis is thought to be a possible risk factor for several chronic eye disease, such as glaucoma, age-related macular degeneration, uveitis, and, recently, diabetic retinopathy. Dysbiosis may cause endothelial disfunction and alter retinal metabolism. This review analyzes the evidence regarding changes in gut microbiota in patients with DR compared with diabetics and healthy controls (HCs). A systematic review was performed on PubMed, Web of Science, and Google Scholar for the following terms: “gut microbiota” OR “gut microbiome” AND “diabetic retinopathy”. Ultimately, 9 articles published between 2020 and 2022 presenting comparative data on a total of 228 T2DM patients with DR, 220 patients with T2DM, and 118 HCs were analyzed. All of the studies found a distinctive microbial beta diversity in DR vs. T2DM and HC, characterized by an altered Firmicutes/Bacteroidetes ratio, a decrease in butyrate producers, and an increase in LPS-expressing and pro-inflammatory species in the Bacteroidetes and Proteobacteria phyla. The probiotic species Bifidobacterium and Lactobacillus were decreased when compared with T2DM. Gut microbiota influence retinal health in multiple ways and may represent a future therapeutic target in DR.

    DOI: 10.3390/life13040968