Therapeutic Advances in Ophthalmology最新文献

The aim of this review article is to describe the specific features of Stargardt disease and ABCA4 retinopathies (ABCA4R) using multimodal imaging and functional testing and to highlight their relevance to potential therapeutic interventions. Standardised measures of tissue loss, tissue function and rate of change over time using formal structured deep phenotyping in Stargardt disease and ABCA4R are key in diagnosis, and prognosis as well as when selecting cohorts for therapeutic intervention. In addition, a meticulous documentation of natural history will be invaluable in the future to compare treated with untreated retinas. Despite the familiarity with the term Stargardt disease, this eponymous classification alone is unhelpful when evaluating ABCA4R, as the ABCA4 gene is associated with a number of phenotypes, and a range of severity. Multimodal imaging, psychophysical and electrophysiologic measurements are necessary in diagnosing and characterising these differing retinopathies. A wide range of retinal dystrophy phenotypes are seen in association with ABCA4 mutations. In this article, these will be referred to as ABCA4R. These different phenotypes and the existence of phenocopies present a significant challenge to the clinician. Careful phenotypic characterisation coupled with the genotype enables the clinician to provide an accurate diagnosis, associated inheritance pattern and information regarding prognosis and management. This is particularly relevant now for recruiting to therapeutic trials, and in the future when therapies become available. The importance of accurate genotype-phenotype correlation studies cannot be overemphasised. This approach together with segregation studies can be vital in the identification of causal mutations when variants in more than one gene are being considered as possible. In this article, we give an overview of the current imaging, psychophysical and electrophysiological investigations, as well as current therapeutic research trials for retinopathies associated with the ABCA4 gene.

Myopia is far beyond its inconvenience and represents a true, highly prevalent, sight-threatening ocular condition, especially in Asia. Without adequate interventions, the current epidemic of myopia is projected to affect 50% of the world population by 2050, becoming the leading cause of irreversible blindness. Although blurred vision, the predominant symptom of myopia, can be improved by contact lenses, glasses or refractive surgery, corrected myopia, particularly high myopia, still carries the risk of secondary blinding complications such as glaucoma, myopic maculopathy and retinal detachment, prompting the need for prevention. Epidemiological studies have reported an association between outdoor time and myopia prevention in children. The protective effect of time spent outdoors could be due to the unique characteristics (intensity, spectral distribution, temporal pattern, etc.) of sunlight that are lacking in artificial lighting. Concomitantly, studies in animal models have highlighted the efficacy of light and its components in delaying or even stopping the development of myopia and endeavoured to elucidate possible mechanisms involved in this process. In this narrative review, we (1) summarize the current knowledge concerning light modulation of ocular growth and refractive error development based on studies in human and animal models, (2) summarize potential neurobiological mechanisms involved in the effects of light on ocular growth and emmetropization and (3) highlight a potential pathway for the translational development of noninvasive light-therapy strategies for myopia prevention in children.

Background: Diabetic retinopathy is a leading cause of visual loss in the working population. Pars plana vitrectomy has become the mainstream treatment option for severe proliferative diabetic retinopathy (PDR) associated with significant vitreous haemorrhage and/or tractional retinal detachment. Despite the advances in surgical equipment, diabetic vitrectomy remains a challenging operation, requiring advanced microsurgical skills, especially in the presence of tractional retinal detachment. Preoperative intravitreal bevacizumab has been widely employed as an adjuvant to ease surgical difficulty and improve postoperative prognosis.Aims: This study aims to assess the effectiveness of preoperative intravitreal bevacizumab in reducing intraoperative complications and improving postoperative outcomes in patients undergoing vitrectomy for the complications of PDR.

Methods: A literature search was conducted using the PubMed, Cochrane, and ClinicalTrials.gov databases to identify all related studies published before 31/10/2020. Prespecified outcome measures were operation time, intraoperative iatrogenic retinal breaks, best-corrected visual acuity in the last follow-up visit, the presence of any postoperative vitreous haemorrhage and the need to re-operate. Evidence synthesis was performed using Fixed or Random Effects models, depending on the heterogeneity of the included studies. Heterogeneity was assessed using Q-statistic and I². Additional meta-regression models, subgroup analyses and sensitivity analyses were performed as appropriate.

Results: Thirteen randomized control trials, with a total of 688 eyes were included in this review. Comparison of the intraoperative data showed that bevacizumab reduced operation time (p < 0.001), minimized iatrogenic retinal breaks (p < 0.001), provided better long-term visual acuity outcomes (p = 0.005), and prevented vitreous haemorrhage (p < 0.001) and the need for reoperation (p = 0.001 < 0.05). Findings were strongly corroborated by additional sensitivity and subgroup analyses.

Conclusion: Preoperative administration of bevacizumab is effective in reducing intraoperative complications and improving the postoperative prognosis of diabetic vitrectomy.PROSPERO registration number: CRD42021219280.

Pediatric uveitis accounts for up to 10% of all uveitis cases, so special attention must be paid to ensure early diagnosis as well as treatment and follow-up of these young patients in order to decrease the risk of possible ocular complications and consequently vision loss. Multimodal imaging has been an effective and important adjunct in the diagnoses and management of uveitis, especially in children. Reviewed here are the currently utilized modalities, advances, as well as their applications in juvenile idiopathic arthritis-associated uveitis, pars planitis, retinal vasculitis, tubulointerstitial nephritis and uveitis syndrome, Behçet disease, Blau syndrome, and Vogt-Koyanagi-Harada syndrome.

Floppy eyelid syndrome (FES) is a frequent eyelid disorder characterized by eyelid laxity that determines a spontaneous eyelid eversion during sleep associated with chronic papillary conjunctivitis and systemic diseases. FES is an under-diagnosed syndrome for the inaccuracy of definition and the lack of diagnostic criteria. Eyelid laxity can result from a number of involutional, local, and systemic diseases. Thus, it is pivotal to use the right terminology. When the increased distractibility of the upper or lower eyelid is an isolated condition, it is defined as 'lax eyelid condition' (LAC). When laxity is associated with ocular surface disorder such as papillary conjunctivitis and dry eyes, it can be referred to as 'lax eyelid syndrome' (LES). However, FES is characterized by the finding of a very loose upper eyelid which everts very easily and papillary tarsal conjunctivitis affecting a specific population of patients, typically male, of middle age and overweight. Obesity in middle-aged male is also recognized as the strongest risk factor in obstructive sleep apnea-hypopnea syndrome, (OSAHS). FES has been reported as the most frequent ocular disorder associated with OSAHS. Patients with FES often complain of non-pathognomonic ocular signs and symptoms such as pain, foreign body sensation, redness, photophobia, and lacrimation. Due to these clinical features, FES is often misdiagnosed while an early recognition might be important to avoid its chronic, distressing course and the associated morbidities. This review provides an updated overview on FES by describing the epidemiology, proposed pathogenesis, clinical manifestations, related ocular, and systemic diseases, and treatment options.

Background: Magnesium has an essential role in glucose metabolism, and hypomagnesaemia is common in diabetes mellitus. However, the relationship between serum magnesium and diabetic retinopathy is poorly understood.

Aim: To determine the association between serum magnesium levels and retinopathy in type 2 diabetic patients with normal renal function and to correlate it with severity of retinopathy.

Methods: This cross-sectional observational study was conducted in a semi-urban tertiary-care teaching hospital. Clinicodemographic profile and serum magnesium levels were determined in patients with type 2 diabetes mellitus (DM) with (group 1) and without (group 2) retinopathy. Serum magnesium levels were correlated with the presence and severity of retinopathy.

Results: Of 104 type 2 DM patients, 50 had retinopathy. Younger age, longer duration of disease and poorer glycaemic control (p < 0.05) were found to be associated with retinopathy. The mean serum magnesium levels in patients with retinopathy and those without retinopathy were 1.63 ± 0.30 mg/dL and 1.76 ± 0.22 mg/dL, respectively (p = 0.029). Reduced serum magnesium was associated with elevated fasting sugars (p = 0.019) and female gender (p = 0.037). On comparative analysis of patients with sight-threatening diabetic retinopathy (STDR), non-STDR and no retinopathy by ANOVA test, patients with STDR had significantly lower serum magnesium (1.55 ± 0.33 mg/dL) (p = 0.031).

Conclusion: Serum magnesium levels were lower in patients with diabetic retinopathy. Patients with STDR had lower serum magnesium compared with those without STDR.

Summary: Serum magnesium, studied extensively for its role in glucose metabolism, was found to be lower in patients with diabetic retinopathy compared with those without retinopathy. Sight-threatening diabetic retinopathy had significantly lower levels of serum magnesium.

The pathogenesis of diabetic macular edema (DME) is complex. Persistently high blood glucose activates multiple cellular pathways and induces inflammation, oxidation stress, and vascular dysfunction. Retinal ganglion cells, macroglial and microglial cells, endothelial cells, pericytes, and retinal pigment epithelium cells are involved. Neurodegeneration, characterized by dysfunction or apoptotic loss of retinal neurons, occurs early and independently from the vascular alterations. Despite the increasing knowledge on the pathways involved in DME, only limited therapeutic strategies are available. Besides antiangiogenic drugs and intravitreal corticosteroids, alternative therapeutic options tackling inflammation, oxidative stress, and neurodegeneration have been considered, but none of them has been currently approved.

Background: The long-term treatment outcomes in Coat's disease - particularly in the era of newer pharmacotherapies such as anti-vascular endothelial growth factor (VEGF) agents and depot steroids - are poorly understood.

Aim: To describe the clinical features and treatment outcomes of 148 eyes with Coats' disease assessed in a referral centre over 30 years.

Materials and methods: We conducted a retrospective chart review of patients diagnosed with Coats' disease between 1 June 1987 and 31 July 2017. The demographic, clinical and treatment data were collected and long-term functional and anatomical outcomes were analysed based on the treatment either with conventional therapy (cryo/laser) or along with adjuvants like intravitreal steroids or anti-VEGFs.

Results: The mean age at presentation was 15.22 years (median 11). Familial exudative vitreoretinopathy was the most common referral diagnosis, 76/148 (51.5%), followed by Coats' disease, 37/148 (25%), and retinoblastoma, 35/148 (23.6%). Stage 3B was most common at presentation (31.8%), followed by 2B (22.3%) and 2A (16.9%). A total of 107 patients were treated either with conventional therapy or in combination with adjuvants. The mean follow-up period was 24.95 months. The visual acuity improved from baseline logMAR 2.17 (Snellen-20/2958) to logMAR 1.88 (Snellen-20/1517) at final follow-up (p = 0.004). The improvement in visual acuity was better when the presenting BCVA was <1 logMAR (Snellen 20/200), p = 0.004. No statistically significant change in BCVA was noted between conventional and adjuvant groups, p = 0.5. However, the final anatomical outcome was good in 78/99 (78.8%) in the conventional group and 45/49 (91.8%) in the adjuvant group, respectively (p = 0.046).

Conclusion: In this series of patients with Coats' disease over three decades, the use of intravitreal steroids or anti-VEGFs as adjuvants resulted in better anatomical outcomes. A better baseline visual acuity, lower stage of the disease, and older age at presentation were found to be the factors leading to favourable visual outcomes.

Summary: In the current series of 148 eyes with Coats' disease, adjuvant treatment with intravitreal steroids or anti-VEGFs resulted in better outcomes as compared with conventional cryotherapy or laser photocoagulation alone. Patients with Coats' disease who had presented with better visual acuity at baseline, lower stage of the disease and older age had better final visual outcomes.

Background: Timely detection of early microvascular changes in patients with prediabetes could help reduce the likelihood of progression of diabetes-related retinal complications.

Aim: To determine early microvascular changes in patients with prediabetes using optical coherence tomography angiography (OCT-A).

Methods: In this single-center retrospective case-control study, macular OCT-A images of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed in non-diabetic controls, and prediabetic and diabetic subjects. A quantitative analysis was performed using ImageJ software of the foveal avascular zone (FAZ) area, acircularity index (AI), perfusion density (PD), and vascular length density (VLD).

Results: A total of 94 eyes of 53 patients were included in this study. The global mean age was 57.7 years, 39.6% men and 60.4% women. In SCP, the mean PD was 0.283 ± 0.15, 0.186 ± 0.720, and 0.186 ± 0.07 in non-diabetic controls, and prediabetic and diabetic groups, respectively. The mean VLD was 8.728 ± 3.425 in non-diabetic controls, 6.147 ± 1.399 in prediabetic group, and 6.292 ± 1.997 in patients with diabetes. The comparison of prediabetic patients and controls shows statistical differences between PD and VLD in both plexus SCP (p = 0.002 and p = 0.001, respectively) and DCP (p = 0.005 and p = 0.002, respectively). The mean area of FAZ in patients with diabetes and normal individuals was 0.281 and 0.196 mm², respectively (p < 0.001). AI was higher in the control group (0.87 ± 0.14) and prediabetic group (0.80 ± 0.17) compared to diabetic patients (0.64 ± 0.19). There were no differences in FAZ area and AI between prediabetic and non-diabetic controls.

Conclusion: PD and VLD demonstrated to be early microvascular changes in prediabetic patients evaluated by OCT-A. No alterations of FAZ were evidenced in this group.