Treatment of macular diseases: an overview of key randomized clinical trials

Macular diseases are traditionally a serious issue in ophthalmology, which has great social impact due to widespread occurrence and significant vision loss, often irreversible. Over the past few decades, the possibilities for the diagnosis and treatment of pathologies of the retina and choroid have been significantly expanded. Randomized clinical trials provided ophthalmologists with valuable information on the natural course and treatment strategies of common retinal diseases from the viewpoint of evidence-based medicine. However, due to the large number of trials conducted, it is often difficult to make an adequate choice of data to be used in daily practice. In this review, we systematize the most valuable randomized clinical trials. To this end, we selected 42 randomized clinical studies conducted between 1979 and 2019 and focused on the treatment of age-related macular degeneration (AREDS 1, AREDS 2, ANCHOR, MARINA, PrONTO, CATT, IVAN, VIEW 1, VIEW 2, EVEREST II, PLANET, SEVEN-UP, ALTAIR, HAWK, HARRIER), choroidal neovascularization of multiple etiology (myopic, post-inflammatory, angioid-streak-related, etc. — RADIANCE, REPAIR, MYRROR, MINERVA), diabetic eye lesions (diabetic retinopathy and diabetic macular edema — ETDRS, DRCR.net Protocols B, I, S and T, RISE, RIDE, VIVID-DME, VISTA-DME, MEAD, FAME), retinal vein occlusions (BVOS, CVOS, SCORE-CRVO, SCORE-BRVO, BRAVO, CRUISE, GALILEO, COPERNICUS, VIBRANT), as well as retinopathy of prematurity (CRYO-ROP, ETROP, RAINBOW). The review summarizes the main results of these studies, which confirm the effectiveness and safety of such treatment methods as antiVEGF and photodynamic therapy, retinal laser photocoagulation, cryotherapy, corticosteroids and nutraceuticals from the viewpoint of evidence-based medicine. For greater clarity, we provide a table summarizing information on each of the randomized clinical trials considered.

The Clinical Contribution of Full-Field Electroretinography and 8-Year Experiences of Application in a Tertiary Medical Center

Electroretinography (ERG) is an important and well-established examination for retinal and visual pathway diseases. This study reviewed the medical records of patients who received full-field ERG (ffERG) at a single medical center between 2012 and 2019, which was an 8-year experience in the clinical contribution of ERG. Based on the indication for scheduling ffERG and the final diagnosis, patients could be classified into six groups: ‘retinal dystrophies’, ‘other retinal or macular diseases’, ‘optic neuropathies’, ‘visual complaints’, ‘systemic diseases’, and ‘others’. A total of 1921 full-field electroretinograms (ffERGs) (1655 patients) were included. The average number of ffERGs performed per year was 262 and the number of annual ffERGs was constant. The ‘retinal dystrophies’ group accounted for 36.5% of the studied population, followed by the ‘other retinal or macular diseases’ group (20.2%). The most common systemic disease was central nervous system disease. The rates of abnormal ffERGs in the ‘systemic diseases’, ‘optic neuropathies’, and ‘visual complaints’ groups were 27.3%, 22.6%, and 10.1%, respectively (p < 0.001). Higher rates were found in patients <20 years old in the ‘systemic diseases’ and ‘optic neuropathies’ groups; epilepsy and optic nerve atrophy were the most common diagnoses, respectively. In brief, by quantifying the functional response in the retina, ffERG is indispensable for diagnosis and prognosis in ophthalmologic and multidisciplinary practice.

Association Between Retinal Sensitivity and the Presence of Quiescent Choroidal Neovascularization in Pachychoroid Diseases

This study was conducted to examine retinal sensitivity (RS) in eyes with pachychoroid diseases and to analyze its association with the presence or absence of quiescent choroidal neovascularization (CNV), that can be protective against retinal dysfunction or atrophy in other macular diseases such as age-related macular degeneration. A total of 12 eyes of 12 patients aged ≥45 years having the characteristic findings of central serous chorioretinopathy but not presenting any exudative changes were included in this study. Choroidal vascular hyper permeability (CVH) was identified by indocyanine green angiography, and the presence or absence of CNV was evaluated by optical coherence tomography angiography. RS at 68 points was examined by microperimetry. The average RS corresponding to within and outside CVH was compared. The association between the difference in RS and the presence or absence of CNV was also analyzed. CNV was detected in six eyes (50%). In eyes without CNV, the RS within CVH was similar compared with that outside CVH. However, in eyes with CNV, the RS within CVH was significantly decreased compared with that outside CVH. Multiple regression analysis revealed the presence of CNV as an independent factor associated with RS. In eyes with pachychoroid diseases, RS decreased within the CVH area under the coexistence of nonexudative CNV.

A Fast Lightweight Based Deep Fusion Learning for Detecting Macula Fovea Using Ultra-Widefield Fundus Images

Macula fovea detection is a crucial prerequisite towards screening and diagnosing macular diseases. Without early detection and proper treatment, any abnormality involving the macula may lead to blindness. However, with the ophthalmologist shortage and time-consuming artificial evaluation, neither accuracy nor effectiveness of the diagnose process could be guaranteed. In this project, we proposed a deep learning approach on ultra-widefield fundus (UWF) images for macula fovea detection. This study collected 2300 ultra-widefield fundus images from Shenzhen Aier Eye Hospital in China. Methods based on U-shape network (Unet) and Fully Convolutional Networks (FCN) are implemented on 1800 (before amplifying process) training fundus images, 400 (before amplifying process) validation images and 100 test images. Three professional ophthalmologists were invited to mark the fovea. A method from the anatomy perspective is investigated. This approach is derived&ensp;from the spatial relationship between macula fovea and optic disc center in UWF. A set of parameters of this method is set based on the experience of ophthalmologists and verified to be effective. Results are measured by calculating the Euclidean distance between proposed approaches and the accurate grounded standard, which is detected by Ultra-widefield swept-source optical coherence tomograph (UWF-OCT) approach. Through a comparation of proposed methods, we conclude that, deep learning approach of Unet outperformed other methods on macula fovea detection tasks, by which outcomes obtained are comparable to grounded standard method.

A Fast Lightweight Based Deep Fusion Learning for Detecting Macula Fovea Using Ultra-Widefield Fundus Images

Macula fovea detection is a crucial prerequisite towards screening and diagnosing macular diseases. Without early detection and proper treatment, any abnormality involving the macula may lead to blindness. However, with the ophthalmologist shortage and time-consuming artificial evaluation, neither accuracy nor effectiveness of the diagnose process could be guaranteed. In this project, we proposed a deep learning approach on ultra-widefield fundus (UWF) images for macula fovea detection. This study collected 2300 ultra-widefield fundus images from Shenzhen Aier Eye Hospital in China. Methods based on U-shape network (Unet) and Fully Convolutional Networks (FCN) are implemented on 1800 (before amplifying process) training fundus images, 400 (before amplifying process) validation images and 100 test images. Three professional ophthalmologists were invited to mark the fovea. A method from the anatomy perspective is investigated. This approach is derived&ensp;from the spatial relationship between macula fovea and optic disc center in UWF. A set of parameters of this method is set based on the experience of ophthalmologists and verified to be effective. Results are measured by calculating the Euclidean distance between proposed approaches and the accurate grounded standard, which is detected by Ultra-widefield swept-source optical coherence tomograph (UWF-OCT) approach. Through a comparation of proposed methods, we conclude that, deep learning approach of Unet outperformed other methods on macula fovea detection tasks, by which outcomes obtained are comparable to grounded standard method.

Macular Findings of Patients on Pentosan Polysulfate Sodium

ABSTRACT Introduction In 2018, a unique maculopathy associated with chronic pentosan polysulfate sodium (PPS) use for the treatment of interstitial cystitis (IC) was described, where the authors detailed macular retinal pigment epithelial abnormalities in six patients. In this paper, a retrospective study of a larger patient pool at one large tertiary retina practice was undertaken to evaluate patients taking PPS and their macular findings. Materials and methods A retrospective chart review was performed on all patients presenting to a single large retina practice between 2011 and 2019. Patient’s macular diagnosis, findings, optical coherence tomography scans, and macular auto-fluorescent scans were assessed. This project was Institutional Review Board (IRB) approved by the St Luke’s Hospital IRB board (St Louis, MO, USA). Results Fifty-five patients were identified as taking PPS for IC. Fifty-three patients were found to have a diagnosis consistent with changes attributable to known macular diseases to include macular degeneration and pattern dystrophies. Two (4%) of fifty-five patients had macular findings suggestive of PPS toxicity. The first was a 58-year-old female with subtle retinal pigment epithelium (RPE) deposits on optical coherence tomography that exhibited hyper-autofluorescence. The second was a 72-year-old female with 14 years of PPS use who exhibited RPE excrescences and parafoveal areas of atrophy. Conclusions Pentosan polysulfate sodium may be the cause of macular findings in a small percentage of patients referred to a tertiary retina practice. Although causation of macular changes with PPS use has yet to be elucidated, clinicians should be aware of this possibility when assessing patients with atypical macular findings. Future longitudinal studies are necessary to evaluate a definitive relationship. This paper should remind all clinicians of the importance of a throughout review of the patient’s medication list as novel toxicities may become apparent years after initial FDA trials. The strength of this study is the larger patient population compared to earlier studies, and the main weaknesses include the retrospective nature of the study, lack of family and genetic testing, and lack of multimodal imaging for all patients.