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    Research Update 583


    Five-year outcomes of digital diabetic eye screening in individuals aged 80 and 85 years.

    Eye (London, England). 2023 May 20

    Thomas K, Albutt N, Hamid A, Wharton H, Jacob S.

    Objective: To assess the incidence of referable diabetic retinopathy (DR) in patients aged 80 and 85 years to determine whether screening interval can be extended safely in this age group.

    Methods: Patients who were aged 80 and 85 years when they attended digital screening during April 2014-March 2015 were included. Screening results at baseline and over the next four years were analysed.

    Results: 1880 patients aged 80 and 1105 patients aged 85 were included. Patients referred to hospital eye service (HES) for DR ranged from 0.7% to 1.4% in the 80-year-old cohort over 5 years. In this cohort a total of 76 (4%) were referred to HES for DR, of which 11 (0.6%) received treatment. Over the course of the follow up (FU), 403 (21%) died. In the 85-year-old cohort, referral to HES for DR each year ranged from 0.1% to 1.3%. In this cohort a total of 27 (2.4%) were referred to HES for DR, of which 4 (0.4%) received treatment. Over the course of follow-up 541(49%) died. All treated cases were for maculopathy in both cohorts and there were no cases of proliferative diabetic retinopathy requiring treatment.

    Conclusion: This study showed that the risk of progression of retinopathy is quite low in this age group and only a small proportion of patients developed referable retinopathy requiring treatment. This suggests relooking at the need for screening and ideal screening intervals in patients aged 80 years and over with no referable DR as they can be potentially classed as a group with low risk of sight loss.

    DOI: 10.1038/s41433-023-02577-x


    Increased risk of Parkinson’s disease among patients with age-related macular degeneration and visual disability: A nationwide cohort study.

    European journal of neurology. 2023 May 27.

    Yoon JM, Lim DH, Youn J, Han K, Kim BS, Jung W, Yeo Y, Shin DW, Ham DI

    Background: The association between Parkinson’s disease (PD) and age-related macular degeneration (AMD) has been shown in previous reports. However, the association between the severity of AMD and PD development is unknown.

    Objectives: We aimed to evaluate the association of AMD with/without visual disability (VD) with the risk of PD occurrence using the National Health Insurance data in South Korea.

    Methods: A total of 4,205,520 individuals, older than or equal to 50 years and without a previous diagnosis of PD, participated in the Korean National Health Screening Program in 2009. AMD was verified using diagnostic codes, and participants with VD were defined as those with loss of vision or visual field defect as certified by the Korean government. The participants were followed up until 31 December, 2019, and incident cases of PD were identified using registered diagnostic codes. The hazard ratio was calculated for groups (control and AMD with/without visual disability) using multivariable adjusted Cox regression analysis.

    Results: In total, 37,507 participants (0.89%) were diagnosed with PD. Among individuals with AMD, the risk of PD development was higher in individuals with VD (aHR 1.35, 95% CI 1.09-1.67) than those without (aHR 1.22, 95% CI 1.15-1.30) compared with controls. Additionally, an increased risk of PD was observed in individuals with AMD compared with controls, regardless of the presence of VD (aHR 1.23, 95% CI 1.16-1.31).

    Conclusions: VD in AMD was associated with the development of PD. This suggests that neurodegeneration in PD and AMD may have common pathways.

    DOI: 10.1111/ene.15896

    Assessment of Parafoveal Diabetic Macular Ischemia on Optical Coherence Tomography Angiography Images to Predict Diabetic Retinal Disease Progression and Visual Acuity Deterioration.

    JAMA Ophthalmology. 2023 May 25:

    Yang D, Tang Z, Ran A, Nguyen TX, Szeto S, Chan J, Wong CYK, Hui V, Tsang K, Chan CKM, Tham CC, Sivaprasad S, Lai TYY, Cheung CY.

    Importance: The presence of diabetic macular ischemia (DMI) on optical coherence tomography angiography (OCTA) images predicts diabetic retinal disease progression and visual acuity (VA) deterioration, suggesting an OCTA-based DMI evaluation can further enhance diabetic retinopathy (DR) management.

    Objective: To investigate whether an automated binary DMI algorithm using OCTA images provides prognostic value on DR progression, diabetic macular edema (DME) development, and VA deterioration in a cohort of patients with diabetes.

    Design, Setting, And Participants: In this cohort study, DMI assessment of superficial capillary plexus and deep capillary plexus OCTA images was performed by a previously developed deep learning algorithm. The presence of DMI was defined as images exhibiting disruption of fovea avascular zone with or without additional areas of capillary loss, while absence of DMI was defined as images presented with intact fovea avascular zone outline and normal distribution of vasculature. Patients with diabetes were recruited starting in July 2015 and were followed up for at least 4 years. Cox proportional hazards models were used to evaluate the association of the presence of DMI with DR progression, DME development, and VA deterioration. Analysis took place between June and December 2022.

    Main Outcomes and Measures: DR progression, DME development, and VA deterioration.

    Results: A total of 321 eyes from 178 patients were included for analysis (85 [47.75%] female; mean [SD] age, 63.39 [11.04] years). Over a median (IQR) follow-up of 50.41 (48.16-56.48) months, 105 eyes (32.71%) had DR progression, 33 eyes (10.28%) developed DME, and 68 eyes (21.18%) had VA deterioration. Presence of superficial capillary plexus-DMI (hazard ratio [HR], 2.69; 95% CI, 1.64-4.43; P < .001) and deep capillary plexus-DMI (HR, 3.21; 95% CI, 1.94-5.30; P < .001) at baseline were significantly associated with DR progression, whereas presence of deep capillary plexus-DMI was also associated with DME development (HR, 4.60; 95% CI, 1.15-8.20; P = .003) and VA deterioration (HR, 2.12; 95% CI, 1.01-5.22; P = .04) after adjusting for age, duration of diabetes, fasting glucose, glycated hemoglobin, mean arterial blood pressure, DR severity, ganglion cell-inner plexiform layer thickness, axial length, and smoking at baseline.

    Conclusions And Relevance: In this study, the presence of DMI on OCTA images demonstrates prognostic value for DR progression, DME development, and VA deterioration.

    DOI: 10.1001/jamaophthalmol.2023.1821


    Impact of anti-VEGF therapy on distinctive retina layers in patients with macular edema secondary to branch retinal vein occlusion.

    BMC Ophthalmology. 2023 May 25;

    Wang H, Wang C, Zhang S, Liu J, Bi X.

    Background: To explore the impact of anti-vascular epithelial growth factor (ant-VEGF) on the thickness of each retinal layer in patients with macular edema (ME) secondary to the branch retinal vein occlusion (BRVO).

    Methods: This retrospective study included patients with ME secondary to monocular BRVO who received anti-VEGF therapy in Ningxia Eye Hospital between January-December 2020.

    Results: Forty-three patients (25 males) were included, with 31 showed > 25% reduction in central retinal thickness (CRT) after anti-VEGF therapy (response group), and the others showed a ≤25% reduction in CRT (no-response group). The response group showed significantly smaller mean changes in the ganglion cell layer (GCL) (after 2 months) and inner plexiform layer (IPL) (after 1, 2, and 3 months) and significantly greater mean changes in the inner nuclear layer (INL) (after 2 and 3 months), outer plexiform layer (OPL) (after 3 months), outer nuclear layer (ONL) (after 2 and 3 months), and CRT (after 1 and 2 months) (all P < 0.05) as compared to the no-response group. The mean change in the thickness of each retinal layer IPL (P = 0.006) between the two groups was significantly different after controlling for a time and with a significant time trend (P < 0.001). Additionally, patients in the response group were more likely to have an improvement in IPL (43.68 ± 6.01 at 1 month and 41.52 ± 5.45 at 2 months vs. 39.9 ± 6.86 at baseline) after anti-VEGF therapy, while those in no response group might show improvement in GCL (45.75 ± 8.24 at 1 month, 40.00 ± 8.92 at 2 months, and 38.83 ± 9.93 at 3 months vs. 49.67 ± 6.83 at baseline).

    Conclusions: Anti-VEGF therapy might help restore the retinal structure and function in patients with ME secondary to BRVO, and those who have a response after anti-VEGF therapy are more likely to improve IPL, while those having no response might show improvement in GCL.

    DOI: 10.1186/s12886-023-02981-7


    Exudative age-related macular degeneration lesion components predicting microperimetric retinal sensitivity during anti-vascular endothelial growth factor treatment.

    Acta Ophthalmologica. 2023 May 25.

    Bygglin H, Immonen I, Luoma A, Hautamäki A.

    Purpose: To analyse the effect of exudative age-related macular degeneration (eAMD) lesion components on retinal sensitivity during anti-vascular endothelial growth factor treatment.

    Methods: Visual acuity, fluorescein and indocyanine green (ICG) angiographies, autofluorescence images, microperimetries and optical coherence tomographies (OCTs) of 24 eyes of 24 patients were prospectively analysed in a 2-year study of pro-re-nata bevacizumab treatment for eAMD. Microperimetries were aligned with the OCTs, angiographies and autofluorescence images. Thicknesses of the neuroretina, pigment epithelial (RPE) elevation, neuroepithelial detachment (NED), subretinal tissue (SRT) and cystic intraretinal fluid were measured under each stimulus site, and areas of type 1 and type 2 macular neovascularizations (MNVs), ICG plaque, haemorrhage and RPE atrophy were identified. The effects and predictive values of lesion components on retinal sensitivity were analysed with multivariate mixed linear models for repeated measurements.

    Results: The overall microperimetric retinal sensitivity increased during the first year (from 10.1 dB at baseline to 11.9 dB at 1 year; p = 0.021, Wilcoxon signed ranks), but remained the same during the second year (11.5 dB, p = 0.301). The baseline lesion components most strongly predicting deteriorated sensitivity at 1 year were RPE atrophy, the area of Type 2 MNV, intraretinal cysts, haemorrhage, Type 1 MNV and retinal thickening >350 μm. NED and RPE elevation had only small effects. At 2 years, the predictive values of the baseline lesion components remained quite unchanged.

    Conclusion: The most powerful predictors of retinal sensitivity loss during 2 years of treatment were RPE atrophy, areas of haemorrhage, the area of MNVs, intraretinal cysts and SRT. RPE elevation and NED had lesser effects.

    DOI: 10.1111/aos.15707

    Hyperreflective foci distribution in eyes with dry age-related macular degeneration with subretinal drusenoid deposits.

    Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2023 May 25

    Kang D, Lee YJ, Nam KT, Choi M, Yun C

    Purpose: To investigate the distribution of hyperreflective foci (HRF) in eyes with dry age-related macular degeneration (AMD).

    Methods: We retrospectively reviewed optical coherence tomography (OCT) images of 58 dry AMD eyes presenting HRF. The distribution of HRF according to the early treatment diabetic retinopathy study area was analyzed according to the presence of subretinal drusenoid deposits (SDDs).

    Results: We classified 32 eyes and 26 eyes into the dry AMD with SDD group (SDD group) and dry AMD without SDD group (non-SDD group), respectively. The non-SDD group had higher prevalence and density of HRF at the fovea (65.4% and 1.71 ± 1.48) than the SDD group (37.5% and 0.48 ± 0.63, P = 0.035 and P < 0.001, respectively). However, the prevalence and density of HRF in the outer circle area of the SDD group (81.3% and 0.11 ± 0.09) were greater than those of the non-SDD group (53.8% and 0.05 ± 0.06, p = 0.025 and p = 0.004, respectively). The SDD group showed higher prevalence and mean densities of HRF in the superior and temporal area than in the non-SDD group (all, p < 0.05).

    Conclusion: HRF distributions in dry AMD varied according to the presence of SDDs. This might support that the degenerative features may be different between dry AMD eyes with and without SDDs.

    DOI: 10.1007/s00417-023-06127-9


    Optical-Quality Assessment of a Miniaturized Intraocular Telescope.

    Journal of clinical medicine. 2023 May 10

    Nepita I, Raimondi R, Piazza S, Diaspro , Vidal-Aroca F, Surdo S, Romano MR

    Age-related macular degeneration (AMD) causes severe vision impairments, including blindness. An option to improve vision in AMD patients is through intraocular lenses and optics. Among others, implantable miniaturized telescopes, which direct light to healthy lateral regions of the retina, can be highly effective in improving vision in AMD patients. Yet, the quality of the restored vision might be sensitive to the optical transmission and aberrations of the telescope. To shed light on these points, we studied the in vitro optical performance of an implantable miniaturized telescope, namely, the SING IMT™ (Samsara Vision Ltd., Far Hills, NJ, USA) designed to improve vision in patients affected by late-stage AMD. Specifically, we measured the optical transmission in the spectral range 350-750 nm of the implantable telescope with a fiber-optic spectrometer. Wavefront aberrations were studied by measuring the wavefront of a laser beam after passing through the telescope and expanding the measured wavefront into a Zernike polynomial basis. Wavefront concavity indicated that the SING IMT™ behaves as a diverging lens with a focal length of -111 mm. The device exhibited even optical transmission in the whole visible spectrum and effective curvature suitable for retinal images magnification with negligible geometrical aberrations. Optical spectrometry and in vitro wavefront analysis provide evidence supporting the feasibility of miniaturized telescopes as high-quality optical elements and a favorable option for AMD visual impairment treatments.

    DOI: 10.3390/jcm12103375


    Ocular manifestations of obstructive sleep apnea: a systematic review and meta-analysis.

    Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2023 May 25

    Bulloch G, Seth I, Zhu Z, Sukumar S, McNab A

    Background: The association of obstructive sleep apnea (OSA) with development of eye diseases is unclear. This current systematic review and meta-analysis attempts to summarize and analyze associations between OSA and ocular disorders in the literature.

    Methods: PubMed, EMBASE, Google Scholar, Web Of Science, and Scopus databases were searched from 1901 to July 2022 in accordance with the Preferred Reporting in Systematic Review & Meta-Analysis (PRISMA). Our primary outcome assessed the association between OSA and the odds of developing floppy eyelid syndrome (FES), glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), retinal vein occlusion (RVO), keratoconus (KC), idiopathic intracranial hypertension (IIH), age-related macular degeneration (AMD), and central serous chorioretinopathy (CSR) through odds ratio calculated at the 95% confidence interval.

    Results: Forty-nine studies were included for systematic review and meta-analysis. The pooled OR estimate was highest for NAION [3.98 (95% CI 2.38, 6.66)], followed by FES [3.68 (95% CI 2.18, 6.20)], RVO [2.71(95% CI 1.83, 4.00)], CSR [2.28 (95% CI 0.65, 7.97)], KC [1.87 (95% CI 1.16, 2.99)], glaucoma [1.49 (95% CI 1.16, 1.91)], IIH [1.29 (95% CI 0.33, 5.01)], and AMD [0.92 [95% CI 0.24, 3.58] All observed associations were significant (p < 0.001) aside from IIH and AMD.

    Conclusion: OSA is significantly associated with NAION, FES, RVO, CSR, KC, and glaucoma. Clinicians should be informed of these associations so early recognition, diagnosis, and treatment of eye disorders can be addressed in at-risk groups, and early referral to ophthalmic services is made to prevent vision disturbances. Similarly, ophthalmologists seeing patients with any of these conditions should consider screening and referring patients for assessment of possible OSA.

    DOI: 10.1007/s00417-023-06103-3


    Limitations of direct-to-consumer genetic testing for age-related macular degeneration.

    European journal of ophthalmology. 2023 May 21

    Shaheen AR, Uhr JH, Sridhar J, Yannuzzi NA.

    The availability of direct-to-consumer genetic testing (DTCGT) for age-related macular degeneration (AMD) provides the public with access to disease risk estimations that may be used to guide lifestyle adjustments. However, AMD development risk is more complex than can be captured by gene mutations alone. The methodologies employed by current DTCGTs to estimate AMD risk vary and are limited in several ways. Genotyping-based DTCGT is biased toward European ancestry and only considers a limited number of genes. Whole genome sequencing based DTCGTs uncovers several genetic variations with unknown relevance, making risk interpretation challenging. In this perspective, we describe the limitations of the DTCGT for AMD.

    DOI: 10.1177/11206721231178054