Correlation between B-scan optical coherence tomography, en face thickness map ring and hyperautofluorescent ring in retinitis pigmentosa patients.

OBJECTIVE: To evaluate and compare the B-scan OCT loss of ellipsoid zone, OCT en face thickness map constriction, and hyperautofluorescent ring constriction in RP patients. METHODS: Retrospective case series study. Forty-eight eyes of 24 RP patients with a parafoveal hyperautofluorescent ring were studied. The diagnosis of RP was established by the presence of rod response impairment and a prevalent decrease of scotopic over photopic responses on electroretinography. The FAF and spectral-domain optical coherence tomography (SD-OCT) images were obtained from 24 patients with RP. The measurements of the EZ line width on B-scan OCT, hyperautofluorescent ring area on FAF, and hyperautofluorescent ring area on en face thickness map were performed by two independent graders. The measurements of these three parameters were correlated. RESULTS: The mean age of study patients was 46 years old (sd = 19). The external and internal FAF rings involving the fovea were identified in all study eyes. The area of the thickness ring decreased at an average rate of 0.5 (sd 0.4) mm2 per year (P < 0.001). The average rate of EZ-line constriction was estimated to be 123 (sd 63) µm per year (P < 0.001). The hyperautofluorescent ring area decreased at an average rate of 0.9 (sd 0.98) mm2 per year (P < 0.001). The strongest correlation was observed between hyperautofluorescent ring area and EZ-line width (r = 0.78). CONCLUSIONS: We observed that the hyperautofluorescent ring area exhibits a faster progression rate than the area of the thickness ring. In addition, we found that the EZ-line width had a high positive correlation with the hyperautofluorescent ring area and a moderate positive correlation with area of the thickness ring.

Fundus autofluorescence and ellipsoid zone (EZ) line width can be an outcome measurement in RHO-associated autosomal dominant retinitis pigmentosa.

PURPOSE: To evaluate the progression of retinitis pigmentosa (RP) due to mutations in rhodopsin (RHO) by measuring the short-wavelength autofluorescence (SW-AF) increased autofluorescence ring and ellipsoid zone (EZ)-line width. METHODS: Fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) images were obtained from 10 patients with autosomal dominant RP due to mutations in the RHO gene. Measurements of ring area on FAF images, as well as the EZ line width on SD-OCT images and horizontal, vertical diameter, were performed by two independent masked graders. RESULTS: The ring area decreased by a rate of 0.6 ± 0.2 mm2 per year. We observed that the EZ line width decreased by an average of 152 ± 37 µm per year, while the horizontal and vertical diameters decreased by 106 ± 35 µm and 125 ± 29 µm per year, respectively. Progression rates were similar between eyes. CONCLUSIONS: We observed SW-AF ring constriction and a progressive loss of EZ line width over time.

Non-paraneoplastic related retinopathy: clinical challenges and review.

Autoimmune retinopathy (AIR) is a rare inflammatory condition characterized by progressive visual loss, abnormalities in visual fields and electroretinographic exams, along with presence of circulating anti-retinal antibodies. There are two main forms of AIR: paraneoplastic AIR (pAIR) and presumed non-paraneoplastic AIR (npAIR). NpAIR is considered a diagnosis of exclusion, since it is typically made after other causes of retinopathy have been investigated and the absence of malignancy is confirmed. Work-up of a npAIR case is challenging since there are no standartizaded protocols for diagnosis and treatment. The treatment regimen may vary from case to case, and it can be best guided by a set of parameters including electrophysiological responses, visual outcomes, and presence of anti-retinal antibodies. The purpose of this review is to summarize the principal clinical features, investigation, and management of npAIR.

Comparison of structural progression between ciliopathy and non-ciliopathy associated with autosomal recessive retinitis pigmentosa.

BACKGROUND: To evaluate and compare the progression of ciliopathy and non-ciliopathy autosomal recessive Retinitis Pigmentosa patients (arRP) by measuring the constriction of hyperautofluorescent rings in fundus autofluorescence (FAF) images and the progressive shortening of the ellipsoid zone line width obtained by spectral-domain optical coherence tomography (SD-OCT). RESULTS: For the ciliopathy group, the estimated mean shortening of the ellipsoid zone line was 259 µm per year and the ring area decreased at a rate of 2.46 mm2 per year. For the non-ciliopathy group, the estimated mean shortening of the ellipsoid zone line was 84 µm per year and the ring area decreased at a rate of 0.7 mm2 per year. CONCLUSIONS: Our study was able to quantify and compare the loss of EZ line width and short-wavelength autofluorescence (SW-AF) ring constriction progression over time for ciliopathy and non-ciliopathy arRP genes. These results may serve as a basis for modeling RP disease progression, and furthermore, they could potentially be used as endpoints in clinical trials seeking to promote cone and rod survival in RP patients.

Multimodal structural disease progression of retinitis pigmentosa according to mode of inheritance.

We analyze disease progression in retinitis pigmentosa (RP) according to mode of inheritance by quantifying the progressive decrease of the ellipsoid zone (EZ) line width on spectral domain optical coherence tomography (SD-OCT) and of the dimensions of the hyperautofluorescent ring on short-wave fundus autofluorescence (SW-FAF). In this retrospective study of 96 patients, average follow-up time was 3.2 ± 1.9 years. EZ line width declined at a rate of -123 ± 8 µm per year, while the horizontal diameter and ring area declined at rates of -131 ± 9 µm and -0.5 ± 0.05 mm2 per year, respectively. Disease progression was found to be slowest for autosomal dominant RP and fastest for X-linked RP, with autosomal recessive RP progression rates between those of adRP and XLRP. EZ line width and ring diameter rates of disease progression were significantly different between each mode of inheritance. By using EZ line width and horizontal diameter as parameters of disease progression, our results confirm that adRP is the slowest progressing form of RP while XLRP is the fastest. Furthermore, the reported rates can serve as benchmarks for investigators of future clinical trials for RP and its different modes of inheritance.

Gene therapy in inherited retinal degenerative diseases, a review.

Hereditary diseases of the retina represent a group of diseases with several heterogeneous mutations that have the common end result of progressive photoreceptor death leading to blindness. Retinal degenerations encompass multifactorial diseases such as age-related macular degeneration, Leber congenital amaurosis, Stargardt disease, and retinitis pigmentosa. Although there is currently no cure for degenerative retinal diseases, ophthalmology has been at the forefront of the development of gene therapy, which offers hope for the treatment of these conditions. This article will explore an overview of the clinical trials of gene supplementation therapy for retinal diseases that are underway or planned for the near future.

Rates of Bone Spicule Pigment Appearance in Patients With Retinitis Pigmentosa Sine Pigmento.

PURPOSE: To determine rate of bone spicule pigmentation appearance in patients with retinitis pigmentosa (RP). DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 240 patients were analyzed for this study. METHODS: A retrospective analysis was conducted at the Electrodiagnostic Clinic at Columbia University Medical Center of all patients' medical records with a diagnosis of RP between July 2017 and January 2018. The medical records of these patients were analyzed to determine whether the patients presented with pigment migration on their first and last visit to our clinic. Among those who did not have bone spicule at first visit, we examined the time to appearance of newly formed bone spicule. The survival distribution was then estimated using the Kaplan-Meier estimator, where the event is bone spicule and time starts at first visit. RESULTS: From the 240 patients analyzed, 213 patients presented with intraretinal pigmentation on the first visit to our clinic, and 27 patients presented without intraretinal pigmentation. Of these 27 patients, 10 patients developed pigmentation by their follow-up, with a median time to appearance of bone spicule of 5.4 years from first visit, according to the Kaplan-Meier estimates. CONCLUSIONS: The timeline of bone spicule pigment appearance in RP has important implications in the natural history characterization of disease progression and application as a biomarker for interventional trials.

Structural disease progression in PDE6-associated autosomal recessive retinitis pigmentosa.

BACKGROUND AND OBJECTIVE: To evaluate the progression of retinitis pigmentosa (RP) caused by mutations in either PDE6A or PDE6B by measuring the progressive constriction of the hyperautofluorescent ring and shortening of the ellipsoid zone (EZ)-line width. PATIENTS AND METHODS: Fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) images were obtained from seven patients with autosomal recessive RP caused by mutations in either PDE6A or PDE6B. Measurements of the EZ line width on SD-OCT images and horizontal, vertical diameter, and ring area on FAF images were performed by two independent graders. The measurements of these four parameters were correlated with one another. RESULTS: We observed that the EZ line width decreased by an average of 91 ± 64 µm per year, while the horizontal and vertical diameters decreased by 103 ± 53 µm and 92 ± 49 µm per year, respectively. The ring area decreased by a rate of 0.3 ± 0.18 mm2 per year. Progression rates were similar for the left eye. CONCLUSIONS: We observed a progressive loss of EZ line width and Short-wavelength fundus autofluorescence (SW-AF) ring constriction over time. These results may serve as reference for better prognostic prediction and patients selection for clinical trials promoting cone rescue.

Caring for Hereditary Childhood Retinal Blindness.

Inherited retinal diseases (IRDs) are a major cause of incurable familial blindness in the Western world. In the pediatric population, IRDs are a major contributor to the 19 million children worldwide with visual impairment. Unfortunately, the road to the correct diagnosis is often complicated in the pediatric population, as typical diagnostic tools such as fundus examination, electrodiagnostic studies, and other imaging modalities may be difficult to perform in the pediatric patient. In this review, we describe the most significant IRDs with onset during the pediatric years (ie, before the age of 18). We describe the pathogenesis, clinical presentation, and potential treatment of these diseases. In addition, we advocate the use of a pedigree (family medical history), electroretinography, and genetic testing as the 3 most crucial tools for the correct diagnosis of IRDs in the pediatric population.

Protein disulfide isomerase redox-dependent association with p47(phox): evidence for an organizer role in leukocyte NADPH oxidase activation.

Mechanisms of leukocyte NADPH oxidase regulation remain actively investigated. We showed previously that vascular and macrophage oxidase complexes are regulated by the associated redox chaperone PDI. Here, we investigated the occurrence and possible underlying mechanisms of PDI-mediated regulation of neutrophil NADPH oxidase. In a semirecombinant cell-free system, PDI inhibitors scrRNase (100 µg/mL) or bacitracin (1 mM) near totally suppressed superoxide generation. Exogenously incubated, oxidized PDI increased (by ~40%), whereas PDIred diminished (by ~60%) superoxide generation. No change occurred after incubation with PDI serine-mutated in all four redox cysteines. Moreover, a mimetic CxxC PDI inhibited superoxide production by ~70%. Thus, oxidized PDI supports, whereas reduced PDI down-regulates, intrinsic membrane NADPH oxidase complex activity. In whole neutrophils, immunoprecipitation and colocalization experiments demonstrated PDI association with membrane complex subunits and prominent thiol-mediated interaction with p47(phox) in the cytosol fraction. Upon PMA stimulation, PDI was mobilized from azurophilic granules to cytosol but did not further accumulate in membranes, contrarily to p47(phox). PDI-p47(phox) association in cytosol increased concomitantly to opposite redox switches of both proteins; there was marked reductive shift of cytosol PDI and maintainance of predominantly oxidized PDI in the membrane. Pulldown assays further indicated predominant association between PDIred and p47(phox) in cytosol. Incubation of purified PDI (>80% reduced) and p47(phox) in vitro promoted their arachidonate-dependent association. Such PDI behavior is consistent with a novel cytosolic regulatory loop for oxidase complex (re)cycling. Altogether, PDI seems to exhibit a supportive effect on NADPH oxidase activity by acting as a redox-dependent enzyme complex organizer.