Clinical, Genotypic, and Imaging Characterization of the Spectrum of ABCA4 Retinopathies.

PURPOSE: To investigate the clinical and genotypic differences in the spectrum of ABCA4-associated retinopathies (ABCA4Rs). DESIGN: Observational, cross sectional case series. PARTICIPANTS: Sixty-six patients (132 eyes) carrying biallelic ABCA4 variants. METHODS: Patients underwent visual acuity measurement and multimodal imaging. Clinical records were reviewed for age at onset, presenting symptoms, genetic variants, and electroretinogram (ERG). Each eye was assigned to a phenotype based on age at onset, imaging and ERG: cone dystrophy-bull's-eye maculopathy (CD-BEM, 40 eyes), cone-rod dystrophy (CRD, 12 eyes), Stargardt disease (SD, 28 eyes), late-onset SD (LO-SD, 38 eyes), and fundus flavimaculatus (14 eyes). Images were analyzed for: peripapillary sparing, retinal pigment epithelium (RPE) atrophy (definitely decreased autofluorescence, DDAF), flecks patterns using autofluorescence; type of atrophy according to Classification of Atrophy Meeting reports, macular and choroidal thickness on OCT; and choriocapillaris flow deficits on OCT angiography. MAIN OUTCOME MEASURES: Primary outcome was to report the demographic, genotypic, and imaging characteristics of the different ABCA4R phenotypes. Secondary objectives included the assessment of imaging biomarkers as outcome measures for clinical trials. RESULTS: Age at onset was lower in CRD (12 ± 8 years) and higher in patients with LO-SD (59 ± 9 years) (all P < 0.01). Central vision loss was a common presenting symptom in CD-BEM and SD, whereas patients with LO-SD primarily complained of difficult dark adaptation. Missense variants were more frequent in CD-BEM, and splice site in CRD and LO-SD (P < 0.05). Peripapillary sparing was absent in 3 eyes with LO-SD (8%). Cone dystrophy-bull's-eye maculopathy eyes typically had complete outer retinal atrophy alterations (98%), whereas CRD and SD eyes showed both complete outer retinal atrophy and complete RPE and outer retinal atrophy (cRORA) (71%-100%). Patients with LO-SD had larger areas of DDAF (100% cRORA) and of choriocapillaris flow deficits (all P < 0.01). Repeatability of DDAF measurements was low for some phenotypes (CD-BEM and CRD) and atrophic areas <7.5 mm2. Resorbed flecks were significantly associated with CRD and LO-SD (P < 0.01). CONCLUSIONS: This research provides a thorough evaluation of the spectrum of ABCA4R. Our findings suggest that certain phenotypes show preferential photoreceptor degeneration (e.g., CD-BEM), whereas others have substantial RPE and choriocapillaris alterations (e.g., LO-SD). We recommend that clinical trial end points take into consideration these imaging features to improve the interpretation of their results. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The retinal neurovascular coupling is impaired in men with vasculogenic erectile dysfunction.

The aim of this study was to study the retinal vessels in patients affected by vasculogenic erectile dysfunction (ED), using dynamic vessel analyzer (DVA). Patients with vasculogenic ED and control subjects were prospectively enrolled to undergo a complete urological and ophthalmologic evaluation, including DVA and structural optical coherence tomography (OCT). The main outcome measures were: (1) arterial dilation; (2) arterial constriction; (3) reaction amplitude (the difference between arterial dilation and constriction); and, (4) venous dilation. Thirty-five patients with ED and 30 male controls were included in the analysis. Mean ± SD age was 52.0 ± 10.8 years in the ED group and 48.1 ± 16.3 years in the control group (p = 0.317). In the dynamic analysis, the arterial dilation was lower in the ED group (1.88 ± 1.50%), as compared with the control group (3.70 ± 1.56%, p < 0.0001). Neither arterial constriction nor venous dilation differed between groups. The reaction amplitude was decreased in ED patients (2.40 ± 2.02%, p = 0.023), compared to controls (4.25 ± 2.20%). In the Pearson correlation analysis, the ED severity, was directly correlated with both reaction amplitude (R = .701, p = 0.004) and arterial dilation (R = .529, p = 0.042). In conclusion, subjects with vasculogenic ED are featured by a significant dysfunction of the retinal neurovascular coupling, which is inversely correlated with ED severity.

Update on Retinal Vein Occlusion.

Retinal vein occlusion represents the second leading cause of retinal vascular disorders, with a uniform sex distribution worldwide. A thorough evaluation of cardiovascular risk factors is required to correct possible comorbidities. The diagnosis and management of retinal vein occlusion have changed tremendously in the last 30 years, but the assessment of retinal ischemia at baseline and during follow-up examinations remains crucial. New imaging techniques have shed light on the pathophysiology of the disease and laser treatment, once the only therapeutic option, is now only one of the possible approaches with antivascular endothelial growth factors and steroid injections being preferred in most cases. Nowadays long-term outcomes are better than those achievable 20 years ago and yet, many new therapeutic options are under development, including new intravitreal drugs and gene therapy. Despite this, some cases still develop sight-threatening complications deserving a more aggressive (sometimes surgical) approach. The purpose of this comprehensive review is to reappraise some old but still valid concepts and to integrate them with new research and clinical data. The work will provide an overview of the disease's pathophysiology, natural history, and clinical features along with a detailed discussion on the advantages of multimodal imaging and of the different treatment strategies with the aim of providing retina specialists with the most updated knowledge in the field.

Morphofunctional analysis of the retina in patients with type 1 diabetes without complications after 30 years of disease.

There is a lack of studies evaluating the sub-clinical retinal changes in patients with long-term type 1 diabetes mellitus (T1DM) and without history of systemic/ocular complications. The aim of this cross-sectional study was to investigate sub-clinical structural and/or vascular retinal changes in patients with long-term (≥30 years) T1DM and without systemic/ocular complications ("happy few" patients) using structural optical coherence tomography (OCT), OCT-angiography and microperimetry. Twelve eyes of 12 consecutive T1DM patients (mean age 52 ± 12 years, mean duration of disease 35 ± 3 years, mean HbA1c level 7.3 ± 2.8%), without micro/macrovascular complications associated with long-standing T1DM, and twelve healthy subjects were consecutively included. No statistically significant differences were disclosed comparing patients and controls for age, sex, best-corrected visual acuity, central macular thickness, and choroidal thickness. Using OCT-angiography, we did not find any significant difference in foveal avascular zone area, perfusion density, vessel length density, and tortuosity. Moreover, no significant differences were disclosed in retinal nerve fiber layer and ganglion cell complex thickness using structural OCT. No differences were disclosed in retinal sensitivity by microperimetry. New diagnostic tools are able to confirm the presence of a particular population of patients with type 1 diabetes who have been completely spared from diabetic retinal complications. The finding of these "happy few" patients could help us to better understand and target future treatments for diabetes.

Multimodal Imaging Assessment of Vascular and Neurodegenerative Retinal Alterations in Type 1 Diabetic Patients without Fundoscopic Signs of Diabetic Retinopathy.

The aim of this cross-sectional case-control study is to investigate the possible presence of vascular/neurodegenerative alterations in the retina of type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy (DR). Thirty-four eyes of 34 consecutive T1DM without DR (mean age 21 ± 2 years) were included. Another cohort of 27 eyes (27 healthy control subjects matched with age and sex) was also recruited. All patients underwent multimodal imaging evaluation using structural optical coherence tomography (OCT), OCT-angiography (OCT-A), dynamic vessel analyzer (DVA) and microperimetry. No significant differences were disclosed comparing diabetics and controls for visual acuity, central macular thickness, and subfoveal choroidal thickness. On retinal nerve fiber layer and ganglion cell complex thickness, no significant differences were disclosed comparing each 3-mm-diameter macular and peripapillary subfield between two groups. Using OCT-A, deep capillary plexus perfusion density (PD) of diabetics was significantly lower compared to control group, whereas PD of other retinal/choriocapillaris plexuses and foveal avascular zone area did not show any significant difference. Using DVA, diabetic eyes revealed a significantly decreased vessel response to flicker light in comparison to controls. No differences were disclosed using microperimetry analysis. Taken together, these results suggest that vascular alterations could be the first detectable retinal change in the development of DR.

Retinal vascular alterations in reticular pseudodrusen with and without outer retinal atrophy assessed by optical coherence tomography angiography.

PURPOSE: To investigate the intraretinal structural and vascular alterations in patients featuring reticular pseudodrusen (RPD), RPD with outer retinal atrophy (ORA), and drusen. DESIGN: Observational cross-sectional study. METHODS: Clinical practice study including 68 eyes of 57 patients (22 eyes of 17 patients with RPD; 24 eyes of 21 patients with RPD+ORA; 22 eyes of 19 patients with drusen). Each patient underwent spectral-domain optical coherence tomography (OCT) and OCT angiography (OCT-A). Measurement of retinal layers' thickness was obtained by the automated segmentation protocol of the Spectralis OCT (Heidelberg Eye Explorer V.1.9.10.0). The superficial capillary plexus (SCP) and the deep capillary plexus (DCP) vessel density, as well as the size of the foveal avascular zone were calculated on 3×3 OCT-A. Main outcome was to compare vessel density at the SCP and DCP among the groups and controls. RESULTS: At the SCP, the vessel density was lower in RPD and RPD+ORA patients with respect to controls (P=0.02 and P=0.003, respectively). At the DCP, meaningful disparity was found between the study groups and the healthy subjects in the vessel density (P<0.001, P=0.04 and P=0.001 for RPD, RDP+ORA and drusen, respectively). The ganglion cell layer (GCL) was thinner in all patients affected either by RPD, RPD+ORA or drusen compared with healthy subjects (P=0.02, P=0.03 and P=0.004, respectively). CONCLUSION: Significant retinal vascular loss is a common feature of patients with non-exudative age-related macular degeneration, more pronounced in those featuring RPD and RPD+ORA. It is associated with retinal thinning, localised particularly at the GCL, compared with controls.

Gender gap in parents' financing strategy for hospitalization of their children: evidence from India.

The 'missing women' dilemma in India has sparked great interest in investigating gender discrimination in the provision of health care in the country. No studies, however, have directly examined discrimination in health-care financing strategies in the case of severe illness of sons versus daughters. In this paper, we hypothesize that households who face tight budget constraints are more likely to spend their meager resources on hospitalization of boys rather than girls. We use the 60th round of the Indian National Sample Survey (2004) and a multinomial logit model to test this hypothesis and to throw some light on this important but overlooked issue. The results reveal that boys are much more likely to be hospitalized than girls. When it comes to financing, the gap in the usage of household income and savings is relatively small, while the gender gap in the probability of hospitalization and usage of more onerous financing strategies is very high. Ceteris paribus, the probability of boys to be hospitalized by financing from borrowing, sale of assets, help from friends, etc. is much higher than that of girls. Moreover, in line with our theoretical framework, the results indicate that the gender gap intensifies as we move from the richest to poorest households.

Quality of life in patients with right- or left-sided brain tumours: literature review.

AIMS: To determine if patients with left- or right-sided hemisphere neoplasm perceive their quality of life (QoL) differently. BACKGROUND: It is not clear whether patients with a lesion in the left hemisphere have a different QoL than those with a lesion in the right hemisphere. (1) In the pre-operative period, patients with a left-sided lesion may have different symptoms according to the position of the tumour. (2) Studies on patients with brain injury demonstrate an association between left frontal lesions and depression: depression can alter the patients' perception of QoL. (3) In the postoperative period, right-handed patients may be disadvantaged by surgical trauma to the motor cortex in the left hemisphere. (4) During the different phases of the disease, the various functions of the two hemispheres may influence the patient's capacity to control QoL; also, as suggested by authors, both the ego and the conscience are mostly located in the left hemisphere. This is the reason that patients with a left-sided lesion may perceive a worse QoL. METHODS: A review of literature was carried out using the Medline database (1966-2007) and CINHAL (1982-2007), using the following Mesh Terms and key words: brain neoplasm, tumour or cancer, hemispheric dominance or laterality or right or left hemisphere, QoL. RESULTS: Seven studies emerged that documented non-homogeneous results and which included different populations. The association between QoL and the side of the lesion was evaluated. CONCLUSIONS: The lack of a substantial number of recent, robust follow-up studies investigating the QoL in patients at different stages of disease and treatment indicates that more research is needed. Relevance to clinical practice. Understanding the QoL in patients with brain neoplasm and the differences between right and left hemisphere sites of the neoplasm can help nurses develop different interventions and offer more guidance for effective clinical intervention.