Proof-of-concept calculations to determine the health-adjusted life-year trade-off between intravitreal Anti-VEGF Injections and transmission of COVID-19
Clin Exp Ophthalmol. 2020 Sep 9.
Matt J Boyd, Daniel A R Scott, David M Squirrell, Graham A Wilson
PMID: 32902023 DOI: 10.1111/ceo.13855
Background: Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease transmission.
Method: We performed probability calculations to estimate COVID-19 infection status and likelihood of disease transmission among neovascular age-related macular degeneration patients and health care workers during anti-VEGF procedures, at various community prevalence levels of COVID-19. We then applied the expected burden of COVID-19 illness and death expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti-VEGF injections were not performed.
Results: Our calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID-19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID-19 prevalence was one per thousand, even when the attack rate in the clinical setting is very high (5-43%).
Conclusion: Unless COVID-19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID-19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.
C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial
Ophthalmology. 2020 Aug 31;S0161-6420(20)30845-9.
Glenn J Jaffe, Keith Westby, Karl G Csaky, Jordi Monés, Joel A Pearlman, Sunil S Patel, Brian C Joondeph, John Randolph, Harvey Masonson, Kourous A Rezaei
PMID: 32882310 DOI: 10.1016/j.ophtha.2020.08.027
Purpose: The complement pathway may play a key role in the pathogenesis of age-related macular degeneration (AMD). The safety and efficacy of avacincaptad pegol (Zimura®), a C5 inhibitor, was assessed in participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study).
Design: International, prospective, randomized, double-masked, sham-controlled, pivotal phase 2/3 clinical trial.
Participants: 286 participants with GA secondary to AMD.
Main outcome measures: The primary efficacy endpoint was the mean rate of change in GA over 12 months measured by fundus autofluorescence (FAF) at three time points: baseline, month 6, and month 12.
Results: The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4% (p-value = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8% (p-value = 0.005) for the avacincaptad pegol 4 mg cohort as compared to their corresponding sham cohorts. The results for both dose groups were statistically significant. Avacincaptad pegol was generally well tolerated after monthly administration over 12 months. There were no avacincaptad pegol related adverse events or inflammation. Further, there were no ocular serious adverse events and no cases of endophthalmitis. The most frequent ocular adverse events were related to the injection procedure.
Conclusions: Intravitreal administration of avacincaptad pegol 2 mg and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 12 month period. As C5 inhibition theoretically preserves C3 activity it may offer additional safety advantages. A second confirmatory pivotal clinical trial is underway to confirm the efficacy and safety of avacincaptad pegol in slowing the GA growth (GATHER2 Study).
Effect of Aflibercept on Diabetic Retinopathy Severity and Visual Function in the RECOVERY Study for Proliferative Diabetic Retinopathy
Ophthalmol Retina. 2020 Aug 31;S2468-6530(20)30350-X.
Ahmed Roshdy Alagorie, Swetha Velaga, Muneeswar Gupta Nittala, Hannah J Yu, Charles C Wykoff, Srinivas R Sadda
PMID: 32882447 DOI: 10.1016/j.oret.2020.08.018
Objective: To evaluate the effect of intravitreal aflibercept on diabetic retinopathy severity and visual function in subjects with proliferative diabetic retinopathy (PDR) without diabetic macular edema (DME). DESIGN PROSPECTIVE: longitudinal, IRB approved multi-center clinical trial, the RECOVERY study (NCT02863354).
Participants: Forty eyes of 40 subjects with PDR and no DME were enrolled in this study. Subjects were randomized into monthly and quarterly 2 mg aflibercept injection cohorts and treated over a period of 12 months.
Methods: All subjects underwent ultra-wide field (UWF) fundus imaging including pseudocolor and fluorescein angiography using an Optos 200Tx device (Optos, Dunfermline, UK).
Main outcome measures: Severity of retinopathy at baseline, month 6, and month 12 was evaluated by certified reading center graders using the diabetic retinopathy severity scale (DRSS). DRSS scores were correlated with the 25-item and 39-item Visual Function Questionnaire scores at baseline and month 12.
Results: Mean age of the subjects was 48.2 years (range 25-75), mean duration of diabetes mellitus was 16.1 years (range 2-36 years) and median HbA1c was 8.8% (IQR 7.4-10). Both monthly and quarterly groups demonstrated a statistically significant regression in DRSS from baseline to month 12 (p < 0.001). The monthly group demonstrated a statistically significant greater regression of DRSS score at the month 6 visit compared to the quarterly group (p= 0.019). However, the difference between the two groups became statistically insignificant at month 12 visit (p= 0.309). There was also no difference in mean VFQ-25 and VFQ-39 composite scores between the monthly and quarterly groups at month 12 (p= 0.947, 0.921, respectively). The improvement in mean VFQ-25 and VFQ-39 composite scores at month 12 was significantly correlated with improvement in DRSS (r= 0.384, p= 0.039; r= 0.361, p= 0.046; respectively).
Conclusions: In this study of eyes with PDR without DME, both monthly and quarterly aflibercept injection groups showed significant improvement in diabetic retinopathy severity at month 12 compared to baseline. The improvement in DRSS was associated with an improvement in VFQ composite score.
Renal Biomarkers for Treatment Effect of Ranibizumab for Diabetic Macular Edema
J Diabetes Res. 2020 Aug 18;2020:7239570.
Ivan Pochou Lai, Wei-Lun Huang, Chung-May Yang, Chang-Hao Yang, Tzyy-Chang Ho, Yi-Ting Hsieh
PMID: 32908935 PMCID: PMC7450296 DOI: 10.1155/2020/7239570
Aims: To investigate the correlations between renal biomarkers and the treatment outcomes of ranibizumab for diabetic macular edema (DME).
Methods: This hospital-based study retrospectively enrolled 88 eyes from 67 patients who had received one-year intravitreal ranibizumab treatment for DME. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) at baseline and during the follow-up period were recorded. BCVA and OCT characteristics at baseline and their changes after ranibizumab treatment were compared between different proteinuria and estimated glomerular filtration rate (eGFR) groups.
Results: Of the 88 eyes studied, those with moderately increased proteinuria had a thicker central subfield foveal thickness (CFT) and a higher proportion of intraretinal cysts than those with no proteinuria (P = 0.012 and 0.045, respectively) at baseline. After one year of ranibizumab treatment, the reduction in CFT was greater in patients with severely increased proteinuria than those with normal to mildly increased proteinuria (P = 0.030). On the other hand, patients with an eGFR <30 tended to have poorer visual improvements than those with normal eGFR (P = 0.044).
Conclusions: After ranibizumab treatment for DME, patients with severe proteinuria tended to gain better anatomical improvement, while those with poor eGFR tended to have poorer visual improvement.
Comparison of 2-Year Outcomes between Intravitreal Ranibizumab and Intravitreal Aflibercept for Diabetic Macular Edema with "Treat-and-Extend" Regimen-Its Usefulness and Problems
J Clin Med. 2020 Sep 2;9(9):E2848.
Shinichiro Chujo, Masahiko Sugimoto, Taku Sasaki, Yoshitsugu Matsui, Kumiko Kato, Atsushi Ichio, Ryohei Miyata, Hisashi Matsubara, Mineo Kondo
PMID: 32887464 DOI: 10.3390/jcm9092848
Background: To compare the effectiveness of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) performed with the treat-and-extend (TAE) regimen on eyes with diabetic macular edema (DME).
Patients and methods: This is a retrospective study of 125 eyes of 125 treatment-naïve DME patients who received anti-VEGF injections at three consecutive monthly intervals as the loading phase. The changes in the best-corrected visual acuity (BCVA), central retinal thickness (CRT), diabetic retinopathy severity scale (DRSS), and total injection numbers were compared between the two anti-VEGF agents.
Results: Among 125 eyes, 26 eyes completed the treatment with the TAE regimen for 24 months (20.8%). Thirteen eyes of 13 patients (mean age, 70.9 ± 6.0 years) received intravitreal injections of 0.5 mg ranibizumab, and 13 eyes of 13 patients (65.9 ± 8.6 years) received 2 mg aflibercept. No significant differences were detected in the baseline demographics. At 24 months, BCVA was significantly improved in both groups; from 0.31 ± 0.19 to 0.10 ± 0.12 logMAR units for IVR and 0.41 ± 0.19 to 0.16 ± 0.28 logMAR units for IVA (p = 1.29 × 10-9). CRT was significantly reduced in both groups; 440.9 ± 69.3 to 307.5 ± 66.4 μm for IVR and 473.9 ± 71.5 to 317.8 ± 71.2 μm for IVA (p = 3.55 × 10-9). No significant differences were detected in the improvements of BCVA, CRT in both groups, and the total injection numbers for 24 months (11.0 ± 1.2 for the IVA group and 12.0 ± 1.0 the IVR group). DRSS was significantly improved in both groups (p = 0.0004 for IVR and p = 0.009 for IVA).
Conclusion: No significant differences were detected in the improvements of BCVA or CRT and injection numbers between the IVR and IVA groups treated with the TAE regimen. These results indicate that the results of the treatment with both agents with the TAE regimen were equally effective, but only 20.8% of patients completed 24 months of continuous treatment with the TAE regimen.
Synopsis: There are no significant differences regarding effectiveness between the IVR and IVA groups treated with the TAE regimen for DME eyes.
DIAGNOSIS & IMAGING
Association of choroidal thickness with intermediate age-related macular degeneration in a Japanese population
Ophthalmol Retina. 2020 Sep 4;S2468-6530(20)30365-1.
Mariko Sasaki, Yoshikazu Ito, Tomoyo Yamazaki, Yasuo Yanagi, Chui Ming Gemmy Cheung, Kaoru Motomura, Setsuko Kawakami, Takamasa Kinoshita, Kenya Yuki, Akiko Hanyuda, Masaru Mimura, Norie Sawada, Shoichiro Tsugane, Kazuo Tsubota
PMID: 32896678 DOI: 10.1016/j.oret.2020.09.001
Purpose: To determine the relationship of choroidal thickness with the early stages of age-related macular degeneration (AMD) and their disease features in a Japanese population.
Design: Cross-sectional survey PARTICIPANTS: A total of 1293 Japanese persons aged 65-86 years residing in the Saku area who underwent eye screening as part of the Japan Public Health Center-based Prospective Study.
Methods: Comprehensive ophthalmic assessment included fundus photography, measurement of intraocular pressure, and determination of refractive status. Optical coherence tomography with enhanced depth imaging mode was performed and subfoveal choroidal thickness was assessed. Multinomial logistic regression models were used to assess the relationships of choroidal thickness with the early stages of AMD, namely early AMD and intermediate AMD, and their disease features, after adjustment for potential confounders.
Main outcome measures: Relationship of choroidal thickness with early AMD, intermediate AMD, and their disease features.
Results: Of the 1293 potential participants, 901 (mean age 73.2 years) had choroidal thickness data, fundus photographs of sufficient quality, and no concomitant retinal disease (including 5 late AMD cases). Mean choroidal thickness was 246.1 μm, and 15.1% had early AMD and 9.0% had intermediate AMD. After adjustment for age, sex, and refractive status, choroidal thickness was positively associated with the presence of intermediate AMD (for each 1-SD micrometer increase, OR: 1.43, 95% CI: 1.13-1.81), whereas no significant association was found with the presence of early AMD. Among intermediate AMD features, choroidal thickness was positively associated with the presence of AMD pigmentary abnormalities (associated with at least medium drusen; for each 1-SD micrometer increase, OR: 2.21, 95% CI: 1.42-3.42), whereas no significant association was found with the presence of large drusen alone. In addition, among large drusen subtypes, choroidal thickness was positively associated with the presence of pachydrusen (for each 1-SD micrometer increase, OR: 1.53, 95% CI: 1.10-2.13). Furthermore, exploratory analysis revealed that choroidal thickness was positively associated with the presence of non-AMD pigmentary abnormalities (for each 1-SD micrometer increase, OR: 1.92, 95% CI: 1.31-2.182).
Conclusions: Choroidal thickness appears to be associated with the pathology of intermediate AMD and its features in Asians.
Fractal analysis of polypoidal choroidal neovascularisation in age-related macular degeneration
Br J Ophthalmol. 2020 Sep 5;bjophthalmol-2020-317011.
Serra Rita, Florence Coscas, Antonio Pinna, Diogo Cabral, Gabriel Coscas, Eric H Souied
PMID: 32892164 DOI: 10.1136/bjophthalmol-2020-317011
Aim: To describe optical coherence tomography angiography (OCTA) features of polypoidal choroidal neovascularisation (PCNV) secondary to age-related macular degeneration.
Methods: A retrospective consecutive series of 51 patients with a diagnosis of PCNV, based on clinical and multimodal imaging, was analysed. All patients with PCNV underwent a comprehensive ophthalmological examination, including fluorescein and indocyanine green angiography, structural optical coherence tomography (OCT) and OCTA. Two blinded retinal specialists carefully reviewed OCTA slabs in order to assess the morphological patterns of PCNV lesions. Furthermore, fractal analysis of PCNV en face images on OCTA, including vascular perfusion density (VPD), fractal dimension (FD) and lacunarity (LAC), was performed.
Results: Fifty-one PCNV eyes were included in the study. In all, the branching vascular network appeared hyper-reflective. Polyps showed two different patterns: in 34/51 (67%) eyes, they corresponded to hypo-reflective structures, whereas in the remaining 17 (33%) eyes, they appeared as hyper-reflective lesions. In all PCNV eyes, mean VPD, FD and LAC were 0.76±0.17%, 1.46±0.12 and 2.4±0.87, respectively. No significant difference was found between PCNVs showing a different OCTA pattern, in terms of quantitative OCTA parameters.
Conclusion: Fractal analysis provides quantitative parameters demonstrating that PCNVs with different OCTA patterns share the same neovascular architecture and branching complexity. These new findings improve our ability to interpret OCTA slabs, opening new areas of discussion about this type of neovascular lesion.
Predicting progression to advanced age-related macular degeneration from clinical, genetic and lifestyle factors using machine learning
Ophthalmology. 2020 Sep 2;S0161-6420(20)30849-6.
Soufiane Ajana, Audrey Cougnard-Grégoire, Johanna M Colijn, Bénédicte Mj Merle, Timo Verzijden, Paulus Tvm de Jong, Albert Hofman, Johannes R Vingerling, Boris P Hejblum, Jean-François Korobelnik, Magda A Meester-Smoor, Marius Ueffing, Hélène Jacqmin-Gadda, Caroline Cw Klaver, Cécile Delcourt, EYE-RISK Consortium
PMID: 32890546 DOI: 10.1016/j.ophtha.2020.08.031
Objective: Current prediction models for advanced age-related macular degeneration (AMD) are based on a restrictive set of risk factors. The objective of this study was to develop a comprehensive prediction model, applying a machine learning algorithm allowing selection of the most predictive risk factors automatically.
Design: Two population-based cohort studies PARTICIPANTS: The Rotterdam Study I (RS-I, training set) included 3838 participants aged 55 years or more, with a median follow-up period of 10.8 years and 108 incident cases of advanced AMD. The ALIENOR study (test set) included 362 participants aged 73 years or more, with a median follow-up period of 6.5 years and 33 incident cases of advanced AMD.
Methods: The prediction model used the bootstrap lasso for survival analysis to select the best predictors of incident advanced AMD in the training set. Predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC).
Main outcome measures: incident advanced AMD (atrophic and/or neovascular), based on standardized interpretation of retinal photographs.
Results: The prediction model retained i) age, ii) a combination of phenotypic predictors (based on the presence of intermediate drusen, hyper-pigmentation in one or both eyes and age-related eye disease study (AREDS) simplified score), iii) a summary genetic risk score based on 49 single nucleotide polymorphisms, iv) smoking, v) diet quality, vi) education, and vii) pulse pressure. The cross-validated AUC estimation in RS-I was 0.92 [0.88-0.97] at 5 years, 0.92 [0.90-0.95] at 10 years and 0.91 [0.88-0.94] at 15 years. In ALIENOR, the AUC reached 0.92 at 5 years [0.87-0.98]. In terms of calibration, the model tended to underestimate the cumulative incidence of advanced AMD for the high-risk groups, especially in ALIENOR.
Conclusions: This prediction model reached high discrimination abilities, paving the way towards making precision medicine for AMD patients a reality in the near future.
Cross-sectional study of the association between cataract surgery and age-related macular degeneration in the era of phacoemulsification in the national health and nutrition examination survey 2005-2008
BMJ Open. 2020 Sep 6;10(9):e032745.
Zhuoting Zhu, Wei Wang, Huan Liao, Stuart Keel, Jian Zhang, Mingguang He
PMID: 32895258 DOI: 10.1136/bmjopen-2019-032745
Objective: To determine the association between cataract surgery and age-related macular degeneration (AMD) in a representative US sample.
Design: Population-based, cross-sectional study.
Setting: The US National Health and Nutrition Examination Survey 2005-2008.
Participants: A total of 5401 participants aged ≥40 years had information in cataract surgery status and gradable retinal photographs for right eyes.
Methods: Cataract surgery status was obtained from questionnaire. Non-mydriatic fundus photographs were collected and AMD status was assessed. The associations between AMD and cataract surgery were evaluated in right eyes using logistic regression models.
Results: Of 338 right eyes with any AMD, 107 right eyes (28.9%) had cataract surgery. After adjusting for multiple variables, there were significant associations between cataract surgery and any AMD (OR 1.36; 95% CI 1.03 to 1.81) or late AMD (OR 2.48; 95% CI 1.01 to 6.09). No significant association was found between cataract surgery and early AMD after adjusting for multiple covariates (OR 1.20; 95% CI 0.91 to 1.59).
Conclusion: Our results suggest that cataract surgery is associated with the presence of AMD, particularly for late AMD. Longitudinal studies investigating the risk and progression of AMD after cataract surgery are needed in the era of phacoemulsification.
Functional Analysis of Rare Genetic Variants in Complement Factor I ( CFI) using a Serum-Based Assay in Advanced Age-related Macular Degeneration
Transl Vis Sci Technol. 2020 Aug 24;9(9):37.
Anuja Java, Peter Baciu, Rafael Widjajahakim, Yun Ju Sung, Jae Yang, David Kavanagh, John Atkinson, Johanna Seddon
PMID: 32908800 PMCID: PMC7453046 DOI: 10.1167/tvst.9.9.37
Purpose: Factor I (FI) is a serine protease regulator of the complement system. Genetic variants in CFI are associated with advanced age-related macular degeneration (AAMD). However, the clinical and functional impact of these variants is unknown. This study assessed the functional significance of rare CFI variants using a serum-based assay.
Methods: Carriers of rare variants with (n = 78) and without AAMD (n = 28), and noncarriers with (n = 49) and without AMD (n = 44) were evaluated. Function of FI was determined by measuring the proteolytic cleavage of C3b to iC3b, using the cofactor protein, Factor H.
Results: CFI variants were categorized into three groups based on antigenic and functional assessments. Type 1 variants (n = 18) in 35 patients with AAMD demonstrated low serum FI levels and a corresponding decrease in FI function. Type 2 variants (n = 6) in 7 individuals demonstrated normal serum FI antigenic levels but reduced degradation of C3b to iC3b. Type 3 variants (n = 15) in 64 individuals demonstrated normal antigenic levels and degradation of C3b to iC3b. However, iC3b generation was low when measured per unit of FI. Thus most rare CFI variants demonstrate either low antigenic levels (type 1) or normal levels but reduced function (types 2 or 3).
Conclusions: Results provide for the first time a comprehensive functional assessment in serum of CFI rare genetic variants and further establish FI's key role in the pathogenesis of AAMD.
Translational relevance: Stratifying patients in the clinic with a rare CFI variant will facilitate screening and targeting patients most likely to benefit from complement therapies.
Geographic distributions of age-related macular degeneration incidence: a systematic review and meta-analysis
Br J Ophthalmol. 2020 Sep 9;bjophthalmol-2020-316820
Miao Zhou, Pei-Chen Duan, Jing-Hong Liang, Xiao-Feng Zhang, Chen-Wei Pan
PMID: 32907810 DOI: 10.1136/bjophthalmol-2020-316820
Purpose: We performed a systematic review and meta-analysis to summarise the geographic distribution of age-related macular degeneration (AMD) incidence.
Methods: Databases including PubMed, Embase and Web of Science were searched for publications of early and late AMD before September 2019. Studies were included if they applied a standardised photographic assessment and classification system. The proportion of participants with AMD in each eligible study was combined to obtain a pooled incidence from all studies using a random effects model. We also assessed sources of potential heterogeneity in the incidence of AMD using meta-regression analyses for both late and early AMD.
Results: Twenty-four population-based studies (70 123 individuals aged 55 years or older) were included in the meta-analysis. The pooled global annual incidences of early and late AMD were 1.59% (95% CI 1.12% to 2.10%) and 0.19% (95% CI: 0.13% to 0.28%), respectively. Individuals of European descent had the highest annual incidence of both early (2.73%, 95% CI 1.63% to 4.57%) and late (0.36%, 95% CI 0.17% to 0.75%) AMD than other ethnic groups. Average age (p=0.001) at baseline, ethnicity (p=0.001), region (p=0.043) and gender (p=0.011) were predictors for incident late AMD, while only average age (p=0.01) at baseline and ethnicity (p=0.025) was associated with incidence of early AMD.
Conclusions: This meta-analysis offers an up-to-date overview of AMD globally, which may provide scientific guidance for the design and implementation of public health strategies such as screening programmes for AMD in both specific geographic locations and ethnic groups, as well as worldwide.
Identification of Key Genes and Pathways Associated with Age-Related Macular Degeneration
J Ophthalmol. 2020 Aug 21;2020:2714746.
Junyu Zhang, Yu Zhou
PMID: 32904543 PMCID: PMC7456487 DOI: 10.1155/2020/2714746
Age-related macular degeneration (AMD) is the leading cause of severe, permanent vision loss among the elderly in the developed world. The cellular and molecular pathogenesis of initiation and development of AMD remain poorly delineated. The limited resources of the human AMD RPE/choroid tissues impeded the extensive study of the disease. To better understand the molecular and pathway changes in human AMD RPE/choroid tissues, we searched the literature and found three independent studies using high-throughput technology to analyze gene expression in 54 human AMD RPE/choroid tissues and 46 age-matched healthy controls. We downloaded these data, pooled them together, and reanalyzed the difference between molecular and pathways by the Ingenuity Pathway Analysis (IPA) database. Totally, 353 differentially expressed genes (DEGs) were identified, among which 181 genes were downregulated and 172 genes were upregulated in RPE/choroid of AMD patients. Furthermore, several significantly enriched biological processes, including cancer, organismal injury and abnormalities, and ophthalmic disease, were identified associated with these DEGs. By analysis of canonical pathway, the phototransduction pathway and atherosclerosis signaling were the top two significant canonical pathways altered in RPE/choroid tissues in human AMD. As expected, several ophthalmic disease-related molecules, including RHO, PDE6A, 3',5'-cyclic-GMP phosphodiesterase, and G protein alpha, were in the central nodes of disease network. The bioinformatics technology combined with the existing high-throughput data was applied to evaluate the underlying key genes and pathways in human AMD tissues, which may predict downstream and upstream biological processes and identify potential therapeutic intervention targets in human AMD.
Biologic Therapy and Treatment Options in Diabetic Retinopathy with Diabetic Macular Edema
Curr Drug Saf. 2020 Sep 2.
Tobias P H Nissen, Henrik Vorum, Kristian Aasbjerg
PMID: 32881673 DOI: 10.2174/1574886315666200902154322
Proliferative diabetic retinopathy and diabetic macular edema can be a potentially sight-threatening disease if not treated correctly. It is directly correlated to the duration of diabetes, and how well managed the patients diabetes is. In the last 15 years, the treatment of diabetic eye disease has taken a quantum leap in methodology due to the group of biological agents named anti-vascular endothelial growth factor (anti-VEGF). The introduction of the first biological agent has revolutionized the treatment, not only in diabetic eye disease but also across most inflammatory eye diseases causing leakage of fluid from the blood vessels i.e. age-related macular degeneration. The availability of these biological agents despite their considerable costs have significantly improved the outcome measured in visual acuity compared to more traditional treatment of diabetic retinopathy in the form of sole laser treatment and glycemic control. The agents demonstrate a favorable safety profile, but if the rarest and most severe side effect occurs, there is a potential total loss of vision. This review aims to make an overview of the current pharmaceutical therapeutic options in the treatment of diabetic macular edema. This includes laser therapy, intravitreal steroids and with a primary focus on intravitreal anti-vascular endothelial growth factors.
Outer Retinal Abnormalities in a Patient with Danon Disease
Retin Cases Brief Rep. 2020 Aug 31.
Ayaka Hasegawa, Kousuke Noda, Akio Fujiya, Kiriko Hirooka, Toshihisa Anzai, Susumu Ishida
PMID: 32890081 DOI: 10.1097/ICB.0000000000001043
Purpose: To report outer retinal abnormalities evaluated using high-resolution imaging modalities in a patient with Danon disease.
Methods: Case report.
Results: A 26-year-old woman, diagnosed with Danon disease based on genetic testing, was referred to our department for further evaluation of ocular findings. Her best-corrected visual acuity was 20/20, and color vision was normal. Fundus examination revealed pigmentary changes consisting of mottled depigmentation and pigmentation in the peripheral retina of both eyes. Spectral-domain optical coherence tomography (SD-OCT) revealed disruptions of the ellipsoid and interdigitation zones, irregularity of the retinal pigment epithelium (RPE), and hyperreflectivity of the outer nuclear layer. In addition, an adaptive optics retinal camera demonstrated the ambiguous macular cone mosaic pattern.
Conclusion: Danon disease is caused by a primary deficiency in lysosomal associated membrane protein 2 (LAMP-2), an important constituent of the lysosomal membrane that plays a crucial role in the process of autophagy. It is possible that the findings of SD-OCT and adaptive optics retinal camera are early changes associated with the accumulation of autophagosomes and/or phagosomes due to LAMP-2 dysfunction in the photoreceptors, eventually followed by outer retinal degeneration, such as thinning of both the photoreceptor and RPE layers at the fovea.