Sustained release gel based on CT image inspection for treatment of diabetes fundus macular lesions.

Currently, slow-release gel therapy is considered to be an effective treatment for fundus macular disease, but the lack of effective evaluation methods limits its clinical application. Therefore, the purpose of this study was to investigate the application and clinical effect of slow-release gel based on CT image examination in the treatment of diabetic fundus macular disease. CT images of fundus macular lesions were collected in a group of diabetic patients. Then the professional image processing software is used to process and analyze the image and extract the key parameters. A slow-release gel was designed and prepared, and applied to the treatment of diabetic fundus macular disease. CT images before and after treatment were compared and analyzed, and the effect of slow-release gel was evaluated. In a certain period of time after treatment, the lesion size and lesion degree of diabetic fundus macular disease were significantly improved by using slow-release gel therapy with CT image examination. No significant adverse reactions or complications were observed during the treatment. This indicates that the slow-release gel based on CT image examination is a safe, effective and feasible treatment method for diabetic fundus macular disease. This method can help improve the vision and quality of life of patients, and provide a new idea and plan for clinical treatment.

Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity.

BACKGROUND: The importance of age on the development of ocular conditions has been reported by numerous studies. Diabetes may have different associations with different stages of ocular conditions, and the duration of diabetes may affect the development of diabetic eye disease. While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality, whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored. It is unclear which types of diabetes are more predictive of ocular conditions. AIM: To examine associations between the age of diabetes diagnosis and the incidence of cataract, glaucoma, age-related macular degeneration (AMD), and vision acuity. METHODS: Our analysis was using the UK Biobank. The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis, and 6689 diabetic participants and 13378 controls for vision analysis. Ocular diseases were identified using inpatient records until January 2021. Vision acuity was assessed using a chart. RESULTS: During a median follow-up of 11.0 years, 3874, 665, and 616 new cases of cataract, glaucoma, and AMD, respectively, were identified. A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age. Individuals with type 2 diabetes (T2D) diagnosed at < 45 years [HR (95%CI): 2.71 (1.49-4.93)], 45-49 years [2.57 (1.17-5.65)], 50-54 years [1.85 (1.13-3.04)], or 50-59 years of age [1.53 (1.00-2.34)] had a higher risk of AMD independent of glycated haemoglobin. T2D diagnosed < 45 years [HR (95%CI): 2.18 (1.71-2.79)], 45-49 years [1.54 (1.19-2.01)], 50-54 years [1.60 (1.31-1.96)], or 55-59 years of age [1.21 (1.02-1.43)] was associated with an increased cataract risk. T2D diagnosed < 45 years of age only was associated with an increased risk of glaucoma [HR (95%CI): 1.76 (1.00-3.12)]. HRs (95%CIs) for AMD, cataract, and glaucoma associated with type 1 diabetes (T1D) were 4.12 (1.99-8.53), 2.95 (2.17-4.02), and 2.40 (1.09-5.31), respectively. In multivariable-adjusted analysis, individuals with T2D diagnosed < 45 years of age [ß 95%CI: 0.025 (0.009,0.040)] had a larger increase in LogMAR. The ß (95%CI) for LogMAR associated with T1D was 0.044 (0.014, 0.073). CONCLUSION: The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

Trichromatic critical flicker frequency as potential visual test in cataract and macula disease patients.

PURPOSE: To investigate the capacity of critical flicker frequency (CFF) in discriminating cataract eyes with or without macula disease using trichromatic flickers, and to develop a model to predict postoperative best corrected visual acuity (BCVA). METHODS: Patients were divided into two groups based on the presence or absence of macular disease. CFF threshold measurements of red (R-CFF), green (G-CFF), and yellow (Y-CFF) flickers were conducted both preoperatively and postoperatively. A generalized estimating equations model (GEE) was employed to examine the relationship between CFF threshold and 3-month postoperative BCVA. RESULTS: A total of 115 eyes were enrolled, with 59 eyes in the cataract alone group and 56 eyes in the cataract with macular disease group completing the follow-up. R-CFF was found to be consistent before and after cataract removal (P = 0.06), even in cases where OCT was not performed successfully (P > 0.05). Y-CFF showed the highest AUC (0.798) for differentiating ocular comorbidities. According to the GEE model, in patients with a CFF threshold below 26 Hz, the odds ratios for achieving a postoperative VA of 20/40 or better were 34.8% for R-CFF, 26.0% for G-CFF, and 24.5% for Y-CFF. CONCLUSION: CFF emerges as a promising tool for predicting postoperative BCVA, providing valuable supplementary insights when fundus examination is obstructed. R-CFF demonstrates the best resistance to cataracts, while Y-CFF exhibits the highest sensitivity both in identifying macular diseases and predicting postoperative BCVA of 20/40 or better.

Eccentric Viewing Training for Age-Related Macular Disease: Results of a Randomized Controlled Trial (the EFFECT Study).

Purpose: Eccentric viewing training for macular disease has been performed for > 40 years, but no large studies including control groups have assessed the benefits of this training. The EFFECT (Eccentric Fixation From Enhanced Clinical Training) study is a large randomized controlled trial of 2 types of eccentric viewing training. Design: Randomized controlled trial. Participants: Two hundred adults with age-related macular disease. Methods: Participants were randomized to either of the following: (1) a control group; (2) a group receiving supervised reading support; (3) a group receiving 3 sessions of training to optimize the use of their own preferred retinal locus; or (4) a group receiving 3 sessions of biofeedback training of a theoretically optimal trained retinal locus. All participants received standard low-vision rehabilitation. Main Outcome Measures: The primary outcome was patient-reported visual task ability measured on the Activity Inventory instrument at goal level. Secondary outcomes included reading performance and fixation stability. Results: There was no difference between groups on change in task ability (F(3,174) = 1.48, P = 0.22) or on any of the secondary outcome measures. Visual acuity and contrast sensitivity fell in all groups, suggesting that disease progression outweighed any benefit of training. Conclusions: Eccentric viewing training did not systematically improve task ability, reading performance, or fixation stability in this study. Our results do not support the routine use of eccentric viewing training for people with progressing age-related macular disease, although this training may help people with end-stage disease. Rehabilitation of an inherently progressive condition is challenging. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Roles and mechanisms of long non-coding RNAs in age-related macular degeneration.

Worldwide, age-related macular degeneration (AMD) is a multifactorial progressive fundus disorder that can cause vision impairment and severe central blindness in older adults. Currently, there are no approved prevention or treatment strategies for non-exudative AMD. While targeting VEGF is the main therapeutic approach to delay the degeneration process in exudative AMD, a significant number of patients show insensitivity or ineffectiveness to anti-VEGF therapy. Despite years of research, the exact mechanism underlying drusen formation and macular atrophy in AMD remains unknown. In the pathogenesis of AMD, lncRNAs play crucial roles, as discussed in this paper. This review focuses on the function of dysregulated lncRNAs and the mechanisms by which specific molecules target these lncRNAs in AMD. The analysis reveals that lncRNAs primarily regulate the progression of AMD by mediating apoptosis, epithelial-mesenchymal transition (EMT), dedifferentiation, and oxidative stress in choroidal vascular endothelial cells, retinal pigment epithelium (RPE) cells, and photoreceptors. Consequently, the regulation of apoptosis, dedifferentiation, EMT, and other processes by lncRNAs has emerged as a crucial focus in AMD research.These findings contribute to our understanding of the role of lncRNAs in AMD and their potential as valuable biomarkers. Furthermore, they highlight the need for further basic and clinical studies to explore the value of lncRNAs as biomarkers and potential therapeutic targets for AMD.

Investigation of satisfaction with short-term outcomes after switching to faricimab to treat neovascular age-related macular degeneration.

PURPOSE: To investigate the outcomes and patient satisfaction at 6-months' follow-up after switching to faricimab to treat neovascular age-related macular degeneration (nAMD) with a treat-and-extend (TAE) regimen. STUDY DESIGN: Retrospective observational study. METHODS: Forty-eight consecutive eyes (48 patients) were switched to faricimab to treat nAMD and followed for 6 months on a TAE regimen. The Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) was administered to patients 6 months after the switch. RESULTS: Best-corrected visual acuity (BCVA) was maintained 6 months after the switch, while the mean (± standard error) central foveal thickness 6 months after the switch (272 ± 14 µm) decreased significantly compared to the time of the switch (372 ± 20 µm) (p < 0.001). The interval between injections 6 months after the switch was 10.45 ± 0.44 weeks, a significant extension from 6.72 ± 0.34 weeks at the switch (p = 0.002). The MacTSQ total score (58.8 ± 1.7) in eyes with a BCVA of 20/40 and better 6 months after the switch was significantly higher compared to that in eyes with a BCVA worse than 20/40 (48.2 ± 1.5) (p < 0.001). The MacTSQ total score (56.8 ± 1.8) in eyes in which a 4 weeks extension of the injection interval was achieved was significantly higher than (49.5 ± 1.9) in eyes without (p < 0.001). CONCLUSION: Switching to faricimab with a TAE regimen seems to maintain the BCVA and extend the injection interval in patients with nAMD, resulting in enhanced satisfaction.

Low rates of optical coherence tomography utilization in the diagnosis and management of retinovascular diseases in a lower middle-income economy.

Background: Optical coherence tomography (OCT) is widely used as the standard of care in evaluating macular and retinovascular diseases. However, the degree of OCT utilization is yet to be researched in a resource-limited country where wide gaps exist in access to healthcare. Aim: To determine the rate of utilization of the OCT in diagnosis, pre-treatment, and post-treatment evaluation of macular and retinovascular diseases treated with intravitreal anti-vascular endothelial growth factor injection (IVI). Patients and Methods: Retrospective, consecutive, and non-comparative case series of eyes diagnosed and treated from Jan 2017 to Jan 2022 for seven macular and retinovascular diseases in five eye clinics in Nigeria. Data extracted include demographics, indication for IVI, eye treated, use or non-use of OCT at the diagnosis (pre-treatment) and after the last IVI (post-treatment), and central macular thickness (CMT) of pre-treatment OCT scans. Results: Seven hundred and forty two eyes were diagnosed with retinovascular and macular diseases (389 right eyes and 353 left eyes).The male to female ratio was 430: 312 eyes. The mean age was, 63.89 years (SD 12.58). Four hundred and fifty two eyes (60.9%) had a pre-treatment OCT, 235 eyes (31.7%) had a post-treatment OCT, and 190 eyes (25.6%) had both pre- and post-treatment OCTs. The rate of pre-treatment OCT varied with the diagnosis (P = 0.000); DME had the highest rate, 74.4%, and HRVO had the lowest, 40%. Post-treatment OCT rate varied with the diagnosis (P = 0.009); non-AMD CNVM had the highest rate, 49.1%, and PCV had the lowest, 24.6%. Pre-treatment OCT rate was influenced by clinic location (P = 0.000); higher in clinics having an OCT. Post-treatment OCT was not influenced by clinic location (P = 0.37). A CRVO eye had the highest maximum CMT (1031 microns) of all the pre treatment eyes and the lowest minimum CMT of all the pre treatment eyes was in a BRVO eye (138 microns). Mean CMT was highest in HRVO (475.33 microns) and lowest in CNVM (307.62 microns). Conclusion: Though OCT is the standard of care for managing retinovascular and macular diseases, this research quantifies the extent of its use in Nigeria and finds it to be low. A post-treatment OCT rate of 32% suggests that urgent steps are required to improve access to OCT for IVI patients.

Characterising the diagnosis of genetic maculopathies in a real-world private tertiary retinal practice in Australia: protocol for a retrospective clinical audit.

PURPOSE: Accurate diagnosis of macular atrophy is paramount to enable appropriate treatment when novel treatments for geographic atrophy and macular dystrophies become available. Genetic testing is useful in distinguishing between the two conditions but is not feasible for the majority of patients in real-world clinical practice. Therefore, we aimed to investigate the potential misdiagnosis of inherited macular dystrophy as age-related macular degeneration (AMD) in real-world ophthalmic practice to assist in the development of guidelines to improve diagnostic accuracy while minimizing genetic testing for targeted patients. METHODS: Retrospective review of the medical records of patients diagnosed with AMD, which included imaging, between 1995 and 2023 from a large multidisciplinary private ophthalmic practice in Australia. We will use a stepwise method to screen for probable cases of macular dystrophy, followed by a consensus review by an expert panel. The outcomes are (1) to determine the potential misdiagnosis rate of macular dystrophy as atrophic AMD by retinal specialists and general ophthalmologists; (2) to identify clinical imaging modalities that are most useful for differentiating macular dystrophy from atrophic AMD; and (3) to establish preliminary guidance for clinicians to improve the diagnosis of macular atrophy from AMD in practice, and thereby target cost-efficient genetic testing. DISCUSSION: Improving the diagnostic accuracy of both AMD and macular dystrophy, while ensuring cost-efficient genetic testing, will improve the targeted treatment of macular diseases when emerging treatments become available.

The Effect of Statins on Ocular Disorders: A Systematic Review of Randomized Controlled Trials.

AIM: Statins have been established in the market not only due to their ability to lower plasma cholesterol levels but also due to their pleiotropic effects. In the literature, there is a controversy regarding the role of statins in ophthalmology. We aimed to systematically address the possible effect of statin therapy on ocular diseases and to identify if there is a beneficial relationship. METHODS: We searched PubMed and Cochrane Library databases up to 31 December 2022 for studies evaluating the effect of statins on ocular diseases. We included all relevant Randomized Control Trials (RCTs) that have been conducted in the adult population. PROSPERO registration number: CRD42022364328. RESULTS: Nineteen RCTs were finally considered eligible for this systematic review, with a total of 28,940 participants. Ten studies investigated the role of simvastatin, suggesting a lack of cataractogenic effect and a possible protective role in cataract formation, retinal vascular diseases, and especially diabetic retinopathy, age-related macular disease progression, and non-infectious uveitis. Four studies investigated lovastatin, showing no cataractogenic effect. Three studies examined atorvastatin, revealing conflicting results regarding diabetic retinopathy. Two studies examined rosuvastatin, indicating a possibly harmful effect on lenses and a significant protective effect on retinal microvasculature. CONCLUSIONS: Based on our findings, we believe that statins have no cataractogenic effect. There are indications that statins may have a protective role against cataract formation, AMD, diabetic retinopathy progression, and non-infectious uveitis. However, our results were insufficient for any robust conclusion. Future RCTs, with large sample sizes, on the current topic are therefore recommended to provide more solid evidence.

Visual function and biofeedback training of patients with central vision loss: a review.

Older individuals with macular diseases, such as age-related macular degeneration, experience central vision loss (CVL) due to degeneration of their photoreceptors and retinal cells. Patients with CVL may experience various vision impairments, including of visual acuity, fixation stability, contrast sensitivity, and stereoacuity. After CVL, most patients develop a preferred retinal locus outside the affected macular region, which serves as a new visual reference. In this review, we provide an overview of the visual function and impairment in individuals with CVL. In addition, the important role of biofeedback training on the visual function and activity of individuals with CVL is also reviewed. Accordingly, the location and development of the preferred retinal loci are discussed. Finally, this review discusses how to conduct biofeedback training to treat individuals with CVL.

Distinctions between Choroidal Neovascularization and Age Macular Degeneration in Ocular Disease Predictions via Multi-Size Kernels ξcho-Weighted Median Patterns.

Age-related macular degeneration is a visual disorder caused by abnormalities in a part of the eye's retina and is a leading source of blindness. The correct detection, precise location, classification, and diagnosis of choroidal neovascularization (CNV) may be challenging if the lesion is small or if Optical Coherence Tomography (OCT) images are degraded by projection and motion. This paper aims to develop an automated quantification and classification system for CNV in neovascular age-related macular degeneration using OCT angiography images. OCT angiography is a non-invasive imaging tool that visualizes retinal and choroidal physiological and pathological vascularization. The presented system is based on new retinal layers in the OCT image-specific macular diseases feature extractor, including Multi-Size Kernels ξcho-Weighted Median Patterns (MSKξMP). Computer simulations show that the proposed method: (i) outperforms current state-of-the-art methods, including deep learning techniques; and (ii) achieves an overall accuracy of 99% using ten-fold cross-validation on the Duke University dataset and over 96% on the noisy Noor Eye Hospital dataset. In addition, MSKξMP performs well in binary eye disease classifications and is more accurate than recent works in image texture descriptors.

The Classification of Common Macular Diseases Using Deep Learning on Optical Coherence Tomography Images with and without Prior Automated Segmentation.

We compared the performance of deep learning (DL) in the classification of optical coherence tomography (OCT) images of macular diseases between automated classification alone and in combination with automated segmentation. OCT images were collected from patients with neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, retinal vein occlusion, cystoid macular edema in Irvine-Gass syndrome, and other macular diseases, along with the normal fellow eyes. A total of 14,327 OCT images were used to train DL models. Three experiments were conducted: classification alone (CA), use of automated segmentation of the OCT images by RelayNet, and the graph-cut technique before the classification (combination method 1 (CM1) and 2 (CM2), respectively). For validation of classification of the macular diseases, the sensitivity, specificity, and accuracy of CA were found at 62.55%, 95.16%, and 93.14%, respectively, whereas the sensitivity, specificity, and accuracy of CM1 were found at 72.90%, 96.20%, and 93.92%, respectively, and of CM2 at 71.36%, 96.42%, and 94.80%, respectively. The accuracy of CM2 was statistically higher than that of CA (p = 0.05878). All three methods achieved AUC at 97%. Applying DL for segmentation of OCT images prior to classification of the images by another DL model may improve the performance of the classification.

Late-Onset Autosomal Dominant Macular Degeneration Caused by Deletion of the CRX Gene.

PURPOSE: To characterize the phenotype observed in a case series with macular disease and determine the cause. DESIGN: Multicenter case series. PARTICIPANTS: Six families (7 patients) with sporadic or multiplex macular disease with onset at 20 to 78 years, and 1 patient with age-related macular degeneration. METHODS: Patients underwent ophthalmic examination; exome, genome, or targeted sequencing; and/or polymerase chain reaction (PCR) amplification of the breakpoint, followed by cloning and Sanger sequencing or direct Sanger sequencing. MAIN OUTCOME MEASURES: Clinical phenotypes, genomic findings, and a hypothesis explaining the mechanism underlying disease in these patients. RESULTS: All 8 cases carried the same deletion encompassing the genes TPRX1, CRX, and SULT2A1, which was absent from 382 control individuals screened by breakpoint PCR and 13 096 Clinical Genetics patients with a range of other inherited conditions screened by array comparative genomic hybridization. Microsatellite genotypes showed that these 7 families are not closely related, but genotypes immediately adjacent to the deletion breakpoints suggest they may share a distant common ancestor. CONCLUSIONS: Previous studies had found that carriers for a single defective CRX allele that was predicted to produce no functional CRX protein had a normal ocular phenotype. Here, we show that CRX whole-gene deletion in fact does cause a dominant late-onset macular disease.

Association of the occurrence of reticular macular diseases with chronic kidney disease based on estimated glomerular filtration rate / 中华实验眼科杂志

Objective:To analyze the relationship between reticular macular disease (RMD) and chronic kidney disease (CKD) by estimated glomerular filtration rate (eGFR).Methods:A cross-sectional study was conducted.Thirty-six consecutive patients (71 eyes) with subretinal drusenoid deposits in at least one eye in optical coherence tomography (OCT) images were enrolled as the RMD group, and 29 consecutive patients (50 eyes) with age-related macular degeneration (AMD) in at least one eye were identified as the non-RMD group at the First Affiliated Hospital of Guangzhou Medical University from February to September 2019.In the same period, 32 healthy volunteers (64 eyes) without eye disease were included as the healthy control group.Serum was collected to calculate the estimated creatinine clearance (eCcr) and the eGFR.The choroidal thickness of macular fovea and the flow density of choroidal capillary layer were measured by OCT.The related factors of RMD and the correlation between CKD and RMD were analyzed by multiple logistic regression analysis.The relationship between eGFR and choroidal capillary blood flow density and foveal choroidal thickness in RMD patients was analyzed by Pearson linear correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (No.2022-50)Results:The eGFR value of the RMD group was (66.40±27.58)ml/(min·1.73 m 2), which was significantly lower than (84.40±20.91)ml/(min·1.73 m 2) of the non-RMD group and (87.64±22.32)ml/(min·1.73 m 2) of the healthy control group (both at P<0.01). eGFR was significantly correlated with the occurrence of RMD ([odds ratio, OR]=0.973, 95%[confidence interval, CI]: 0.954-0.992, P=0.005). Subgroup analysis showed that this correlation was significant in the CKD stage (eGFR<60 ml/[min·1.73 m 2]) ( OR=6.482, 95% CI: 1.543-27.236, P=0.011). The choroidal thickness of the macular fovea in the RMD group was significantly lower than that of the non-RMD grup and healthy control group (both at P<0.01). In the RMD group, no significant correlation was found between the choroidal thickness of the macular fovea and eGFR ( r=0.138, P>0.05), and the flow density of choroidal capillary layer was moderately positively correlated with eGFR ( r=0.457, P<0.05). Conclusions:There is a correlation between the occurrence of CKD and RMD, which may be due to the confounding effect of the systemic microcirculation disorder.

Release of ranibizumab using a porous poly(dimethylsiloxane) capsule suppressed laser-induced choroidal neovascularization via the transscleral route.

The administration of anti-vascular endothelial growth factor drugs in the posterior eye segment with sustained release through less invasive methods is a challenge in the treatment of age-related macular disease. We developed a flexible capsule device using porous poly(dimethylsiloxane) (PDMS) that was able to release ranibizumab. The porous PDMS sheet was fabricated by salt-leaching of a micro-sectioned PDMS sheet containing salt microparticles. Observation with scanning electron microscopy revealed that the pore densities could be adjusted by the concentration of salt. The in vitro release study showed that the release rate of fluorescein isothiocyanate-tagged albumin could be adjusted based on the pore density of the porous PDMS sheet. Ranibizumab could be released in a sustained-release manner for 16 weeks. The device was implanted on the sclera; its efficacy in terms of the suppression of laser-induced choroidal neovascularization (CNV) in rats was compared with that of monthly intravitreal injections of ranibizumab. At 8 and 18 weeks after implantation, the CNV area was significantly reduced in rats that received the ranibizumab-releasing device compared with those that received the placebo device. However, although monthly intravitreal injections of ranibizumab reduced CNV for 8 weeks, this reduction was not sustained for 18 weeks. In conclusion, we demonstrated a novel controlled-release device using a porous PDMS sheet that could suppress CNV via a less invasive transscleral route versus intravitreal injections. This device may also reduce the occurrence of side effects associated with frequent intravitreal injections.

Subretinal drusenoid deposits: An update.

A wide spectrum of phenotypic manifestations characterizes age-related macular degeneration (AMD). Drusen is considered the hallmark of AMD and is located underneath the retinal pigment epithelium (RPE). In contrast, subretinal drusenoid deposits (SDDs), also known as reticular pseudodrusens, are located in the subretinal space, on top of the RPE. SDDs are poorly detected by clinical examination and color fundus photography. Multimodal imaging is required for their proper diagnosis. SDDs are topographically and functionally related to rods. SDDs cause a deep impairment in retinal sensitivity and dark adaptation. SDDs are dynamic structures that may grow, fuse with each other, or regress over time. An intermediate step in some eyes is the development of an acquired vitelliform lesion. The presence of SDD confers an eye a high risk for the development of late AMD. SDD leads to macular neovascularization, particularly type 3, geographic atrophy, and outer retinal atrophy.

New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy-Beyond Classical Gene Candidates.

Central areolar choroidal dystrophy (CACD) is a rare hereditary disease that mainly affects the macula, resulting in progressive and usually profound visual loss. Being part of congenital retinal dystrophies, it may have an autosomal dominant or recessive inheritance and, until now, has no effective treatment. Given the shortage of genotypic information about the disease, this work systematically reviews the literature for CACD-causing genes. Three independent researchers selected 33 articles after carefully searching and filtering the Scielo, Pubmed, Lilacs, Web of Science, Scopus, and Embase databases. Mutations of six genes (PRPH2, GUCA1A, GUCY2D, CDHR1, ABCA4, and TTLL5) are implicated in the monogenic dominant inheritance of CACD. They are functionally related to photoreceptors (either in the phototransduction process, as in the case of GUCY2D, or the recovery of retinal photodegradation in photoreceptors for GUCA1A, or the formation and maintenance of specific structures within photoreceptors for PRPH2). The identified genetic variants do not explain all observed clinical features, calling for further whole-genome and functional studies for this disease. A network analysis with the CACD-related genes identified in the systematic review resulted in the identification of another 20 genes that may influence CACD onset and symptoms. Furthermore, an enrichment analysis allowed the identification of 13 transcription factors and 4 long noncoding RNAs interacting with the products of the previously mentioned genes. If mutated or dysregulated, they may be directly involved in CACD development and related disorders. More than half of the genes identified by bioinformatic tools do not appear in commercial gene panels, calling for more studies about their role in the maintenance of the retina and phototransduction process, as well as for a timely update of these gene panels.

Drug sustained release from degradable drug-loaded in-situ hydrogels in the posterior eye: A mechanistic model and analytical method.

Biodegradable in-situ hydrogels as drug release carriers injected into the eye can treat Neovascular age-related macular degeneration (NV-AMD). Obviously, the biodegradation behavior of hydrogels affects the drug diffusion process in the eye, which can influence the drug concentration distribution and development in the macula. Herein, the intraocular diffusion process of the drugs which are released from the biodegradable hydrogel was studied by using finite element method, with the effect of the biodegradation behavior of hydrogels on the drug release process was considered. The effects of the initial average mesh size, rate constant of biodegradation, and position of hydrogels on the drug release process were analyzed. The results showed that the biodegradation behavior of hydrogels decreases the drug release rate by gradually expanding the mesh size, prolonging the duration of drug treatment in the macula. The biodegradable hydrogels' position, initial mesh size, and biodegradation rate constant also affect drug delivery. Different locations of hydrogels denote different distances between the drug and macula, which affects the diffusion time and further influence the macular drug concentration. The initial mesh size alters the initial drug release rate, which affects the duration of hydrogels' drug release process and drug concentration and duration in the macula. The hydrogel degradation rate affects the development of its mesh size, which affects the drug diffusion in hydrogels, and further affects the drug concentration in the macular region.

Macular Optical Coherence Tomography before Cataract Surgery.

PURPOSE: To determine the benefits of performing preoperative spectral domain optical coherence tomography (SD-OCT) and to identify occult macular pathologies in patients scheduled for routine cataract surgery. METHODS: In this cross-sectional study, macular SD-OCT scans were performed on all patients with clinically undetected macular abnormalities who were scheduled for cataract surgery. Patients with clinically evident macular abnormalities were excluded from the study. A retinal specialist reviewed all the scans. The severity of the cataract was determined using the Oxford Clinical Cataract Classification and Grading System. RESULTS: Of the 598 evaluated cases, 33 patients (5.52%) had an occult macular abnormality. The most common pathology found in these patients was idiopathic epiretinal membrane, which was detected in 17 eyes (51.52%), followed by vitreomacular traction in nine eyes (27.27%), and dry age-related macular degeneration in four eyes (12.12%). Full-thickness macular holes and a lamellar macular hole were found in two patients (6.06%) and one patient (3.03%), respectively. The frequency of cortical cataracts was significantly lower in patients without macular lesions (P = 0.012) than in those with macular lesions. Multivariate logistic regression analysis revealed that age >70 years (P = 0.025 and odds ratio [OR] =11.12), smoking history (P = 0.043 and OR = 3.43), and hypertension were independently associated with occult macular lesions. The surgical plan was changed for five patients (0.83%). CONCLUSIONS: Macular SD-OCT can be used to detect occult macular lesions and provide useful information about a macula before cataract surgery. Although preoperative OCT found macular abnormalities in about 5% of patients with presumed normal fundus examination, it can result in changing the surgical plan in 0.83% of all patients.

Non-transfer Deep Learning of Optical Coherence Tomography for Post-hoc Explanation of Macular Disease Classification.

Deep transfer learning is a popular choice for classifying monochromatic medical images using models that are pretrained by natural images with color channels. This choice may introduce unnecessarily redundant model complexity that can limit explanations of such model behavior and outcomes in the context of medical imaging. To investigate this hypothesis, we develop a configurable deep convolutional neural network (CNN) to classify four macular disease conditions using retinal optical coherence tomography (OCT) images. Our proposed non-transfer deep CNN model (acc: 97.9%) outperforms existing transfer learning models such as ResNet-50 (acc: 89.0%), ResNet-101 (acc: 96.7%), VGG-19 (acc: 93.3%), Inception-V3 (acc: 95.8%) in the same retinal OCT image classification task. We perform post-hoc analysis of the trained model and model extracted image features, which reveals that only eight out of 256 filter kernels are active at our final convolutional layer. The convolutional responses of these selective eight filters yield image features that efficiently separate four macular disease classes even when projected onto two-dimensional principal component space. Our findings suggest that many deep learning parameters and their computations are redundant and expensive for retinal OCT image classification, which are expected to be more intense when using transfer learning. Additionally, we provide clinical interpretations of our misclassified test images identifying manifest artifacts, shadowing of useful texture, false texture representing fluids, and other confounding factors. These clinical explanations along with model optimization via kernel selection can improve the classification accuracy, computational costs, and explainability of model outcomes.