Advanced Retinitis Pigmentosa Research Articles

Evaluation of Full-Field Stimulus Threshold Test Results in Retinitis Pigmentosa: Relationship with Full-Field Electroretinography, Multifocal Electroretinography, Optical Coherence Tomography, and Visual Field.

The full-field stimulus threshold (FST) test was developed to evaluate the efficacy and safety of treatments of hereditary retinal diseases. In this study we performed the FST test in patients with retinitis pigmentosa (RP) and compared the results with findings from other ophthalmological tests. The study included 51 intermediate and advanced RP patients and 21 normal subjects. All patients and controls underwent routine examination and ophthalmological tests including visual field, optical coherence tomography, full-field and multifocal electroretinography (mfERG), and FST tests. During FST testing, the perception thresholds of retina to the white, blue, and red FST were determined in decibels. The mean age of the patients and the controls were 35.2 and 33.5 years, respectively. For all RP patients, no response was obtained on full-field ERG. All subjects were able to perform reliable FST tests. The mean values of visual acuity and central macular thickness were significantly lower and visual field mean deviation values were significantly higher in the RP group than the controls. When we evaluated the mfERG findings, the mean P1 wave amplitudes in all rings were significantly lower and the mean peak times were significantly longer in RP patients than controls. In comparisons of FST test results, the mean values for white, blue, red and the difference between blue-red thresholds were significantly lower in the RP group than the control group. The FST test is a fast and a reliable exam which can be done in subjects with poor visual acuity and reduced visual field. The results of this study confirm that the FST test can measure retinal sensitivity in severely affected RP subjects with flat flash ERG.

Diagnostic Challenges in ABCA4-Associated Retinal Degeneration: One Gene, Many Phenotypes

(1) Purpose: ABCA4-associated retinal degeneration (ABCA4-RD) is a phenotypically diverse disease that often evades diagnosis, even by experienced retinal specialists. This may lead to inappropriate management, delayed genetic testing, or inaccurate interpretation of genetic testing results. Here, we illustrate the phenotypic diversity of ABCA4-RD using a series of representative cases and compare these to other conditions that closely mimic ABCA4-RD. (2) Methods: Genetically confirmed ABCA4-RD cases with representative phenotypes were selected from an inherited retinal disease cohort in Singapore and compared to phenocopies involving other retinal diseases. (3) Results: ABCA4-RD phenotypes in this series included typical adolescent-onset Stargardt disease with flecks, bull’s eye maculopathy without flecks, fundus flavimaculatus, late-onset Stargardt disease, and severe early-onset Stargardt disease. Phenocopies of ABCA4-RD in this series included macular dystrophy, pattern dystrophy, cone dystrophy, advanced retinitis pigmentosa, Leber congenital amaurosis, drug toxicity, and age-related macular degeneration. Key distinguishing features that often suggested a diagnosis of ABCA4-RD were the presence of peripapillary sparing, macular involvement and centrifugal distribution, and a recessive pedigree. (4) Conclusions: ABCA4-RD demonstrates a remarkable phenotypic spectrum that makes diagnosis challenging. Awareness of the clinical spectrum of disease can facilitate prompt recognition and accurate diagnostic testing.

Chromatic pupillometry isolation and evaluation of intrinsically photosensitive retinal ganglion cell-driven pupillary light response in patients with retinitis pigmentosa.

The pupil light response (PLR) is driven by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). We aimed to isolate ipRGC-driven pupil responses using chromatic pupillometry and to determine the effect of advanced retinitis pigmentosa (RP) on ipRGC function. A total of 100 eyes from 67 patients with advanced RP and 18 healthy controls (HCs) were included. Patients were divided into groups according to severity of visual impairment: no light perception (NLP, 9 eyes), light perception (LP, 19 eyes), faint form perception (FFP, 34 eyes), or form perception (FP, 38 eyes). Pupil responses to rod-weighted (487 nm, -1 log cd/m2, 1 s), cone-weighted (630 nm, 2 log cd/m2, 1 s), and ipRGC-weighted (487 nm, 2 log cd/m2, 1 s) stimuli were recorded. ipRGC function was evaluated by the postillumination pupil response (PIPR) and three metrics of pupil kinetics: maximal contraction velocity (MCV), contraction duration, and maximum dilation velocity (MDV). We found a slow, sustained PLR response to the ipRGC-weighted stimulus in most patients with NLP (8/9), but these patients had no detectable rod- or cone-driven PLR. The ipRGC-driven PLR had an MCV of 0.269 ± 0.150%/s and contraction duration of 2.562 ± 0.902 s, both of which were significantly lower than those of the rod and cone responses. The PIPRs of the RP groups did not decrease compared with those of the HCs group and were even enhanced in the LP group. At advanced stages, ipRGC responses gradually became the main component of the PLR. Chromatic pupillometry successfully isolated an ipRGC-driven PLR in patients with advanced RP. This PLR remained stable and gradually became the main driver of pupil contraction in more advanced cases of RP. Here, we present baseline data on ipRGC function; we expect these findings to contribute to evaluating and screening candidates for novel therapies.

Detailed Evaluation of Chromatic Pupillometry and Full-Field Stimulus Testing to Assess Ultralow Vision in Retinitis Pigmentosa

PurposeNovel therapeutic options, such as regenerative medicine and gene therapy, are now emerging as viable treatment options for patients with severe visual impairments, such as retinitis pigmentosa (RP). Gradable assessment of patients’ visual function is essential to consider treatment options and to evaluate treatment outcomes; however, evaluation of visual function in patients with advanced low vision is often challenging because of patients’ poor and sometimes unpredictable responses. In this study, we attempted to accurately assess visual capabilities and disease stage in patients with RP with a visual acuity (VA) of ≤ 0.01.DesignRetrospective analysis of visual function indicators, including VA, retinal thickness, full-field stimulus testing (FST), and chromatic pupillometry.SubjectsOverall, 43 patients (84 eyes) with advanced RP with a VA of ≤ 0.01 visited Kobe City Eye Hospital from 2019 to 2021.MethodsHierarchical (multilevel) Bayesian modeling was used to estimate individual eye’s pupil response and FST threshold, taking into account the ambiguity and randomness often observed in patients with ultralow vision. Using the estimated ability obtained from each test, the correlation between each test and retinal thickness was further analyzed to make a comprehensive assessment of the data.Main Outcome MeasuresVisual acuity, retinal thickness, FST threshold, and pupil diameter change to different light stimuli.ResultsFull-field stimulus testing and pupillometry measurements were moderately correlated with VA but exhibited a wide range of values within the same VA groups. Full-field stimulus testing was not correlated with central retinal thickness at counting fingers/hand motion VA range and seemed to reflect overall remaining photoreceptor function, including peripheral retina. Pupillometry may be able to distinguish between different levels of inner retinal function.ConclusionsThe combination of pupillometry and FST allowed for graded evaluation of visual function within patients grouped in the same VA groups in patients with advanced RP with ultralow vision.Financial Disclosure(s)Proprietary or commercial disclosure may be found after the references. Novel therapeutic options, such as regenerative medicine and gene therapy, are now emerging as viable treatment options for patients with severe visual impairments, such as retinitis pigmentosa (RP). Gradable assessment of patients’ visual function is essential to consider treatment options and to evaluate treatment outcomes; however, evaluation of visual function in patients with advanced low vision is often challenging because of patients’ poor and sometimes unpredictable responses. In this study, we attempted to accurately assess visual capabilities and disease stage in patients with RP with a visual acuity (VA) of ≤ 0.01. Retrospective analysis of visual function indicators, including VA, retinal thickness, full-field stimulus testing (FST), and chromatic pupillometry. Overall, 43 patients (84 eyes) with advanced RP with a VA of ≤ 0.01 visited Kobe City Eye Hospital from 2019 to 2021. Hierarchical (multilevel) Bayesian modeling was used to estimate individual eye’s pupil response and FST threshold, taking into account the ambiguity and randomness often observed in patients with ultralow vision. Using the estimated ability obtained from each test, the correlation between each test and retinal thickness was further analyzed to make a comprehensive assessment of the data. Visual acuity, retinal thickness, FST threshold, and pupil diameter change to different light stimuli. Full-field stimulus testing and pupillometry measurements were moderately correlated with VA but exhibited a wide range of values within the same VA groups. Full-field stimulus testing was not correlated with central retinal thickness at counting fingers/hand motion VA range and seemed to reflect overall remaining photoreceptor function, including peripheral retina. Pupillometry may be able to distinguish between different levels of inner retinal function. The combination of pupillometry and FST allowed for graded evaluation of visual function within patients grouped in the same VA groups in patients with advanced RP with ultralow vision.

Intermediate Uveitis in Retinitis Pigmentosa Associated with a Novel Homozygous Splice Site Mutation in PRPF8.

The manifestation of intermediate uveitis (IU) in patients with retinitis pigmentosa (RP) is uncommon and poses diagnostic and management challenges. In this case, we describe the clinical features and management outcomes in an RP patient with a novel homozygous splice site mutation in PRPF8. A 21-year-old male presented with unilateral decrease of vision in the right eye for 1 week. Retinal dystrophy features were present in the left eye. After 2 weeks of topical steroid therapy, near-total resolution of IU was achieved and vision improved to 20/30. Signs of (RP) were present bilaterally, with the right eye more affected than the left. Genetic testing indicated a novel homozygous c. 3061-6_3061-3del mutation in the PRPF8 gene. IU in young patients with RP can be effectively treated with a short course of topical steroids, sparing the need for systemic immunosuppressives. After the improvement in IU, the right eye showed more advanced RP changes.

Human retinal organoids harboring IMPG2 mutations exhibit a photoreceptor outer segment phenotype that models advanced retinitis pigmentosa.

Interphotoreceptor matrix proteoglycan 2 (IMPG2) mutations cause a severe form of early-onset retinitis pigmentosa (RP) with macular involvement. IMPG2 is expressed by photoreceptors and incorporated into the matrix that surrounds the inner and outer segments (OS) of rods and cones, but the mechanism of IMPG2-RP remains unclear. Loss of Impg2 function in mice produces a mild, late-onset photoreceptor phenotype without the characteristic OS loss that occurs in human patients. We generated retinal organoids (ROs) from patient-derived induced pluripotent stem (iPS) cells and gene-edited embryonic stem cells to model human IMPG2-RP invitro. All ROs harboring IMPG2 mutations lacked an OS layer, in contrast to isogenic controls. Subsequent protein analyses revealed that this phenotype arises due to a loss of IMPG2 expression or its inability to undergo normal post-translational modifications. We hypothesized that loss of IMPG2 function destabilizes the interphotoreceptor matrix and renders the OS vulnerable to physical stressors, which is accentuated in the tissue culture environment. In support of this mechanism, transplantation of IMPG2 mutant ROs into the protected subretinal space of immunocompromised rodents restored OS production. Beyond providing a robust platform to study IMPG2-RP, this human RO model system may serve a broader role in honing strategies to treat advanced photoreceptor-based diseases.

Visual task-related functional and structural magnetic resonance imaging for the objective quantitation of visual function in patients with advanced retinitis pigmentosa.

PurposeThe objective quantitation of visual function in patients with advanced retinitis pigmentosa (RP) presents a difficult challenge due to the weak visual function of these patients. This study utilized magnetic resonance imaging (MRI) to assess the function and structure of the visual cortex (VC) in patients with RP and quantitatively categorize them.Materials and MethodsTwenty-three patients with RP and ten healthy controls (HCs) were enrolled for MRI examinations. The patients were divided into form perception (FP) and no form perception (NFP) groups. Participants underwent structural MRI scans, and two visual task functional MRI scans were performed using stimuli, including white flash and black and white checkerboard patterns. Eight regions of interest (ROIs) were studied. In structural MRI, the gray matter volume (GMV) was compared in the ROIs. In the two visual tasks, the response intensity and functional connectivity (FC) of ROIs were also compared separately. Correlation analysis was performed to explore the correlations between the structural and functional parameters.ResultsIn the structural analysis, the GMV in Brodmann areas 17, 18, and 19 of the FP and NFP groups was significantly lower than that of HCs. Regarding the functional data, the response intensity in the VC of both the FP and NFP groups was significantly lower than that in HCs. The response in Brodmann areas 17, 18, and 19 obtained using the pattern stimulus was significantly lower in the NFP group than in the FP group. For the FC comparison, the FP and NFP groups exhibited significantly lower values in several pathways than the HCs, and FC in the ipsilateral V1–contralateral V1 pathway in the flash task was significantly lower in the NFP group than in the FP group. A positive correlation between response intensity and GMV was observed in Brodmann areas 17, 18, and 19 in both flash and pattern visual tasks.ConclusionMagnetic resonance imaging was an effective tool to objectively and quantitatively evaluate the visual function of patients with advanced RP. Response intensity and FC were effective parameters to distinguish FP and NFP patients. A positive correlation between response intensity and GMV was observed in the VC.

Artificial vision: the effectiveness of the OrCam in patients with advanced inherited retinal dystrophies.

PurposeTo investigate the impact of the OrCam MyEye 2.0 (OrCam) on the quality of life and rehabilitation needs in patients with advanced retinitis pigmentosa (RP) or cone‐rod dystrophies (CRD). The OrCam is a wearable low‐vision aid that converts visual information to auditive feedback (e.g. text‐to‐speech, barcode and facial recognition).MethodsPatients with a clinical diagnosis of RP (n = 9, 45%) or CRD (n = 11; 55%), and a best‐corrected visual acuity of ≤20/400 Snellen were invited to participate in this study. Questionnaires were administered at baseline and after 5.2 (standard deviation ± 1.5) weeks, which included the Dutch version of the National Eye Institute Visual Functioning Questionnaire (NEI‐VFQ), the Participation and Activity Inventory (PAI) and the OrCam Function Questionnaire (OFQ).ResultsFollowing OrCam testing, significant improvements were observed in the ‘near activities’ subscale of the NEI‐VFQ (p < 0.001); the ‘visual functioning’ subscale of the re‐engineered NEI‐VFQ (p = 0.001); the ‘reading’ rehabilitation goal of the PAI (p = 0.005) and the overall score of the OFQ (p < 0.001). The observed changes in questionnaire scores did not differ between phenotypes. Advantages and limitations of the OrCam were reported by patients. Three patients (15%) continued rehabilitation with the OrCam after completion of this study.ConclusionsThe OrCam mainly improves reading domains in patients with advanced stages of RP or CRD. Further improvements in the OrCam are needed to address current limitations, which may enhance its utility for patients with RP or CRD.

Flap technique-assisted surgeries for advanced retinitis pigmentosa complicated with macular hole: a case report and literature review

BackgroundFull-thickness macular hole (FTMH) is a rare complication in retinitis pigmentosa (RP) patients and may increase intraoperative challenges. Furthermore, lens capsular flap transplantation and inverted internal limiting membrane (ILM) flap were reported to close complicated FTMH successfully. Here, we present a case of bilateral advanced RP complicated by a FTMH treated with a novel lens capsular flap transplantation and inverted internal limiting membrane flap.Case presentationA 46-year-old presented to our hospital with a complaint of progressively blurred vision and metamorphopsia in both eyes. Spectral-domain optical coherence tomography revealed a FTMH with retinoschisis in the right eye and another FTMH in the left eye. ILM peeling with inverted ILM flap technique was performed on the right eye and ILM peeling with anterior lens capsular flap technique was performed on the left eye. Post-operative follow-up showed successful closure of the FTMH and improved vision in both eyes.ConclusionsIn our present case, flap-assisted techniques for retinitis pigmentosa with macular hole result in excellent visual and anatomic outcomes.

Functional Dynamics of Deafferented Early Visual Cortex in Glaucoma.

In advanced retinitis pigmentosa with retinal lesions, the lesion projection zone (LPZ) in the early visual cortex can be driven during visual tasks, while it remains unresponsive during passive viewing. We tested whether this finding translates to advanced glaucoma, a major cause of acquired blindness. During visual stimulation, 3T fMRI scans were acquired for participants with advanced glaucoma (n = 4; age range: 51–72) and compared to two reference groups, i.e., advanced retinitis pigmentosa (n = 3; age range: 46–78) and age-matched healthy controls with simulated defects (n = 7). The participants viewed grating patterns drifting in 8 directions (12 s) alternating with uniform gray (12 s), either during passive viewing (PV), i.e., central fixation, or during a one-back task (OBT), i.e., reports of succeeding identical motion directions. As another reference, a fixation-dot task condition was included. Only in glaucoma and retinitis pigmentosa but not in controls, fMRI-responses in the lesion projection zone (LPZ) of V1 shifted from negative for PV to positive for OBT (p = 0.024 and p = 0.012, respectively). In glaucoma, these effects also reached significance in V3 (p = 0.006), while in V2 there was a non-significant trend (p = 0.069). The general absence of positive responses in the LPZ during PV underscores the lack of early visual cortex bottom-up plasticity for acquired visual field defects in humans. Trends in our exploratory analysis suggesting the task-dependent LPZ responses to be inversely related to visual field loss, indicate the benefit of patient stratification strategies in future studies with greater sample sizes. We conclude that top-down mechanisms associated with task-elicited demands rather than visual cortex remapping appear to shape LPZ responses not only in retinitis pigmentosa, but also in glaucoma. These insights are of critical importance for the development of schemes for treatment and rehabilitation in glaucoma and beyond.

Choroideremia Gene Therapy.

Choroideremia Gene Therapy.

Restoring Color Perception to the Blind: An Electrical Stimulation Strategy of Retina in Patients with End-stage Retinitis Pigmentosa

Bioelectronic retinal prostheses that stimulate the remaining inner retinal neurons, bypassing degenerated photoreceptors, have been demonstrated to restore some vision in patients blinded by retinitis pigmentosa (RP). These implants encode luminance of the visual scene into electrical stimulation, however, leaving out chromatic information. Yet color plays an important role in visual processing when it comes to recognizing objects and orienting to the environment, especially at low spatial resolution as generated by current retinal prostheses. In this study, we tested the feasibility of partially restoring color perception in blind RP patients, with the aim to provide chromatic information as an extra visual cue. Case series. Seven subjects blinded by advanced RP and monocularly fitted with an epiretinal prosthesis. Frequency-modulated electrical stimulation of retina was tested. Phosphene brightness was controlled by amplitude tuning, and color perception was acquired using the Red, Yellow, Green, and Blue (RYGB) hue and saturation scaling model. Brightness and color of the electrically elicited visual perception reported by the subjects. Within the tested parameter space, 5 of 7 subjects perceived chromatic colors along or nearby the blue-yellow axis in color space. Aggregate data obtained from 20 electrodes of the 5 subjects show that an increase of the stimulation frequency from 6 to 120 Hz shifted color perception toward blue/purple despite a significant inter-subject variation in the transition frequency. The correlation between frequency and blue-yellow perception exhibited a good level of consistency over time and spatially matched multi-color perception was possible with simultaneous stimulation of paired electrodes. No obvious correlation was found between blue sensations and array placement or status of visual impairment. These findings present a strategy for the generation and control of color perception along the blue-yellow axis in blind patients with RP by electrically stimulating the retina. It could transform the current prosthetic vision landscape by leading in a new direction beyond the efforts to improve the visual acuity. This study also offers new insights into the response of our visual system to electrical stimuli in the photoreceptor-less retina that warrant further mechanistic investigation.

FLVCR1-related disease as a rare cause of retinitis pigmentosa and hereditary sensory autonomic neuropathy

FLVCR1 encodes for a transmembrane heme exporter protein and it is known to cause a rare form of syndromic retinitis pigmentosa: posterior column ataxia with retinitis pigmentosa. Recently, the FLVCR1-associated phenotype has been expanded with sporadic reports of hereditary sensory-autonomic neuropathy or non-syndromic retinitis pigmentosa. Here, we report a 23-year- old female with early onset hypomyelinating sensory-autonomic neuropathy and retinitis pigmentosa. Both features were present since childhood. The patient developed signs of advanced retinitis pigmentosa by the age of 10 years leading to legal blindness after the age of 18. Following candidate gene panel testing, which was negative, whole exome sequencing revealed compound heterozygous pathogenic FLVCR1 variants: NM_014053.3: c.3G > T; p.(Met1?) and NM_014053.3: c.730G > A; p.(Gly244Ser), the latter variant is novel. In this report we highlight the association of retinitis pigmentosa with hypomyelinating sensory-autonomic neuropathy, which could be underdiagnosed due to variable severity. To summarize, the phenotypic heterogeneity of FLVCR1 variants is broad and should include retinitis pigmentosa along with range of neurological features.

A novel, wearable, electronic visual aid to assist those with reduced peripheral vision.

PurposeTo determine whether visual-tactile sensory substitution utilizing the Low-vision Enhancement Optoelectronic (LEO) Belt prototype is suitable as a new visual aid for those with reduced peripheral vision by assessing mobility performance and user opinions.MethodsSighted subjects (n = 20) and subjects with retinitis pigmentosa (RP) (n = 6) were recruited. The LEO Belt was evaluated on two cohorts: normally sighted subjects wearing goggles to artificially reduce peripheral vision to simulate stages of RP progression, and subjects with advanced visual field limitation from RP. Mobility speed and accuracy was assessed using simple mazes, with and without the LEO Belt, to determine its usefulness across disease severities and lighting conditions.ResultsSighted subjects wearing most narrowed field goggles simulating most advanced RP had increased mobility accuracy (44% mean reduction in errors, p = 0.014) and self-reported confidence (77% mean increase, p = 0.004) when using the LEO Belt. Additionally, use of LEO doubled mobility accuracy for RP subjects with remaining visual fields between 10° and 20°. Further, in dim lighting, confidence scores for this group also doubled. By patient reported outcomes, subjects largely deemed the device comfortable (100%), easy to use (92.3%) and thought it had potential future benefit as a visual aid (96.2%). However, regardless of severity of vision loss or simulated vision loss, all subjects were slower to complete the mazes using the device.ConclusionsThe LEO Belt improves mobility accuracy and therefore confidence in those with severely restricted peripheral vision. The LEO Belt’s positive user feedback suggests it has potential to become the next generation of visual aid for visually impaired individuals. Given the novelty of this approach, we expect navigation speeds may improve with experience.

Identification of two novel RHO mutations in Chinese retinitis pigmentosa patients

Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinal diseases with more than 80 identified causative genes to date. Mutations in the RHO (rhodopsin, OMIM, 180380) are the most common cause of autosomal dominant RP (adRP) worldwide. RHO is also one of the few RP genes that can cause autosomal recessive RP (arRP). To explore the frequency of RP mutations in Chinese populations, panel-based NGS (next-generation sequencing) screening and Sanger sequencing validation were performed for RP patients from 72 unrelated Chinese families. Here we reported the identified mutations only in the RHO gene. Our results showed that 4 mutations in RHO were detected in 5 (6.94%) of the 72 RP families, including two known missense mutations, c.158C > G (p.P53R) and c.551A > C (p.Q184P), and two novel mutations, c.34delC (p.P12NA) and c.82C > T (p.Q28X). The c.34delC (p.P12NA) mutation was detected in heterozygous state in one patient with intermediate RP phenotype. The c.82C > T (p.Q28X) mutation was found in a homozygous state in one proband with advanced RP phenotype at the age of 32. Clinical examination of the heterozygous carriers of c.82C > T (p.Q28X) in that family showed that the father at the age of 60s experienced no symptoms of RP and normal fundus examinations but displayed reduced electroretinography (ERG) and abnormal visual field. The sister and brother at the age of 30s showed no typical aspects of RP phenotypes. Our results not only expand the mutation spectrum of the RHO gene, but also suggest that the 2 null mutations might play minor dominant effects, leading to less severe and slower retinal degeneration in heterozygous state and more severe phenotype in homozygous state.

POSTERIOR STAPHYLOMAS IN EYES WITH RETINITIS PIGMENTOSA WITHOUT HIGH MYOPIA.

To describe features of posterior staphylomas in nonhighly myopic eyes with retinitis pigmentosa (RP). The retrospective observational case series study included patients with RP and an axial length of <26.5 mm and searched for eyes with posterior staphylomas. All study participants underwent fundus photography and optical coherence tomography. The study identified 13 eyes of 7 patients with a narrow macular staphyloma. Mean age was 40.9 ± 17.9 years (range 9-62 years) and mean axial length was 24.90 ± 0.69 mm. The staphyloma edges corresponded to the margin between the retinal atrophic area in the fundus midperiphery and the relatively unaffected fundus center. On vertically orientated optical coherence tomography images, the staphyloma edges showed a slight inward protrusion of the sclera and a ring-like localized choroidal thinning with choroidal rethickening in direction toward the fovea and toward the periphery of the fundus. The upper and lower staphyloma edges did not differ in steepness. The thickness of the subfoveal choroid (138.6 m ± 50.1 µm) was thinner than the normal range after adjusting for age and axial length in all eyes. Two eyes with advanced RP in the macula showed a subfoveal choroidal thickness of 95 µm and 88 µm. Narrow macular staphylomas can occur in nonhighly myopic eyes with RP and, in contrast to staphylomas in highly myopic eyes, show a less marked thinning of the subfoveal choroid. The occurrence of posterior staphylomas in nonhighly myopic eyes with RP may provide hints to unravel the etiology of posterior staphyloma formation.

The influence of visual field position induced by a retinal prosthesis simulator on mobility.

Our aim is to develop a new generation of suprachoroidal-transretinal stimulation (STS) retinal prosthesis using a dual-stimulating electrode array to enlarge the visual field. In the present study, we aimed to examine how position and size of the visual field-created by a retinal prosthesis simulator-influenced mobility. Twelve healthy subjects wore retinal prosthesis simulators. Images captured by a web camera attached to a head-mounted display (HMD) were processed by a computer and displayed on the HMD. Three types of artificial visual fields-designed to imitate phosphenes-obtained by a single (5 × 5 electrodes; visual angle, 15°) or dual (5 × 5 electrodes ×2; visual angle, 30°) electrode array were created. Visual field (VF)1 is an inferior visual field, which corresponds to a dual-electrode array implanted in the superior hemisphere. VF2 is a superior visual field, which corresponds to a single-electrode array implanted in the inferior hemisphere. VF3 is a superior visual field, which corresponds to a dual-electrode array implanted in the inferior hemisphere. In each type of artificial visual field, a natural circular visual field (visual angle, 5°) which imitated the vision of patients with advanced retinitis pigmentosa existed at the center. Subjects were instructed to walk along a black carpet (6m long × 2.2m wide) without stepping on attached white circular obstacles. Each obstacle was 20cm in diameter, and obstacles were installed at 40-cm intervals. We measured the number of footsteps on the obstacles, the time taken to complete the obstacle course, and the extent of head movement to scan the area (head-scanning). We then compared the results recorded from these 3 types of artificial visual field. The number of footsteps on obstacles was lowest in VF3 (One-way ANOVA; P = 0.028, Fisher's LSD; VF 1 versus 3 P = 0.039, 2 versus 3 P = 0.012). No significant difference was observed for the time to complete the obstacle course or the extent of head movement between the 3 visual fields. The superior and wide visual field (VF3) obtained by the retinal prosthesis simulator resulted in better mobility performance than the other visual fields.

Correlation between Visual Function and Structural Characteristics of the Macula in Advanced Retinitis Pigmentosa

We aimed to correlate the visual function and structural characteristics of the retina and choroid in advanced retinitis pigmentosa (RP) patients. A cross-sectional, retrospective review was conducted of medical records of 149 RP patients who reported visual field constriction on a central 30-2 Humphrey visual field chart. Using spectral domain-optical coherence tomography, central foveal thickness (CFT), ellipsoid zone (EZ) length, macular volume (MV), and submacular choroidal thickness (SMChT) were measured. A control cohort (68 eyes of 68 patients) was included for comparing the macular structure. Quantitative correlations between visual function indices [visual field index (VFI) and best-corrected visual acuity (BCVA)] and structural indices (CFT, EZ length, and SMChT) were evaluated. Mean age was 46.3 ± 15.5 years; mean illness duration was 60.7 ± 60.0 months. SMChT was thinner than that in normal controls. Per Pearson’s correlation, BCVA and VFI exhibited a progressive worsening related to age and disease duration. In multivariate linear regression, BCVA and VFI were significantly correlated with CFT, EZ length, and MV at the central 1-mm area. Among RP patients with visual field constriction within 30°, VFI and BCVA closely correlate with the degree of retinal structural change, including the CFT, EZ length, and MV. SMChT uniformly decreased in this study population and exhibited no significant correlation with BCVA or VFI degree.

The development of white matter structural changes during the process of deterioration of the visual field

Emerging evidence suggests that white matter plasticity in the adult brain is preserved after sensory and behavioral modifications. However, little is known about the progression of structural changes during the process of decline in visual input. Here we studied two groups of patients suffering from advanced retinitis pigmentosa with specific deterioration of the visual field: patients who had lost their peripheral visual field, retaining only central (“tunnel”) vision, and blind patients with complete visual field loss. Testing of these homogeneous groups made it possible to assess the extent to which the white matter is affected by loss of partial visual input and whether partially preserved visual input suffices to sustain stability in tracts beyond the primary visual system. Our results showed gradual changes in diffusivity that are indicative of degenerative processes in the primary visual pathway comprising the optic tract and the optic radiation. Interestingly, changes were also found in tracts of the ventral stream and the corticospinal fasciculus, depicting a gradual reorganisation of these tracts consequentially to the gradual loss of visual field coverage (from intact perception to partial vision to complete blindness). This reorganisation may point to microstructural plasticity underlying adaptive behavior and cross-modal integration after partial visual deprivation.

Correlation between Transient Pupillary Light Reflex and Retinal Function Impairment in Patients with Retinitis Pigmentosa.

Purpose To investigate the relationship between transient pupillary light reflex (PLR) and visual function in patients with retinitis pigmentosa (RP). Methods A retrospective study was performed with 137 eyes of 73 patients with RP. Transient pupillary light reflex was measured by the vision monitor system (MonColor; Metrovision, France). Dark-adapted transient PLRs were elicited by four specific levels of stimulus luminance (−5, −3, −1, and 0 log cd/m2, blue or white light). Best-corrected visual acuity (BCVA) was recorded based on Early Treatment Diabetic Retinopathy Study (ETDRS) acuity charts. Fixation stability and retinal sensitivity of radial 10° areas were measured with microperimetry. The retinal sensitivity (RS) was divided into central RS (fovea and radial 1° areas) and peripheral RS (radial 3° and 5° areas from the fovea). The patients were further classified into 2 groups (P1 > 75% and P1 < 75%) according to fixation stability. Spearman's correlation was performed to identify significant associations between BCVA, fixation stability, RS, and PLR. Results Under the stimuli of the same color light, relative pupillary constriction (RPC), latency, or velocity of constriction in the same patients was statistically different in multiple luminance, respectively. Under the same luminance, blue light induced greater RPC and velocity (except for −3 log cd/m2) than white light. Most patients showed varying degrees of threshold elevation and visual function deficiency. Besides, there was a statistically significant difference in the distribution of BCVA, MRS, or fixation stability under different thresholds. The correlation between pupillary constrictive area (PCA) and retinal sensitivity was mainly determined by the peripheral region. Moreover, patients with stable fixation showed a greater correlation between PCA and RS. Conclusion PLR induced by specific colors and luminance may serve as a promising clinical approach for assessing and monitoring rod function in advanced RP patients.