Effect of silicone oil versus gas tamponade on macular layer microstructure after pars plana vitrectomy for macula on rhegmatogenous retinal detachment.

PURPOSE: To analyze structural changes in the macular retinal layers and sub-foveal choroidal thickness (SFCT) in eyes after macula-on rhegmatogenous retinal detachment (RRD) repair by pars plana vitrectomy with either silicone oil (SO) or gas tamponade, and the effect of these changes on visual acuity. PATIENTS AND METHODS: Retrospective study which included 26 eyes in the SO Group and 32 in the Gas Group. Optical coherence tomography (OCT) scans of the affected eyes were obtained before surgery, and 3 months after PPV in the Gas Group, and during silicone oil in situ and 3 months after SO removal, in the SO Group. Qualitative assessment of photoreceptor layer and foveal contour, along with quantitative assessment of macular retinal thickness and SFCT was performed. Postoperative OCT macular microstructural changes were recorded and correlated to corrected distance visual acuity (CDVA). Intraocular pressure (IOP) was measured preoperative and at 3 months post operative. RESULTS: There was a 2-line loss (from 20/28 preoperatively to 20/40 at final follow-up) of CDVA in the SO Group (p=0.051), while there was no statistically significant change in CDVA in the Gas Group (p=0.786). There was no significant correlation between CDVA loss and duration of silicon tamponade (r=-0.031, p=0.893). There was a statistically significant increase in IOP from its baseline to final follow-up of 0.7 mmHg in the SO Group (p=0.023) while there was no statistically significant change in IOP in the Gas Group. During silicone oil tamponade, there was approximately 11% and 5% of retinal and sub-foveal choroidal thinning respectively, which was moderately resolved following silicone oil removal. 20% (5/24) of eyes in the SO Group had qualitative flattening of foveal contour during SO tamponade that resolved after SO removal. CONCLUSION: Thinning of the macula was noticed after macula-on RRD repair with SO tamponade. Such thinning was only partially reversible after the removal of SO.

LEPREL1 -RELATED GIANT RETINAL TEAR DETACHMENTS MIMIC THE PHENOTYPE OF OCULAR STICKLER SYNDROME.

PURPOSE: To describe the features of retinal detachments and high myopia in patients with novel pathogenic variants in LEPREL1 and report a possible association with nephropathy. METHODS: Retrospective study of 10 children with biallelic LEPREL1 pathogenic variants. Data included ophthalmic features, surgical interventions, and genetic and laboratory findings. RESULTS: 10 patients (8 females) from three families with homozygous (2) or compound heterozygous (1) variants in LEPREL1 were included. At presentation, mean age was 9.9 ± 2.6 years. Mean axial length was 28.9 ± 1.9 mm and mean refraction was -13.9 ± 2.8 diopters. Bilateral posterior subcapsular cataracts were present in eight patients (80%), with lens subluxation in five eyes of three patients (30%). Rhegmatogenous retinal detachments (RRD), associated with giant retinal tears (GRT), developed in seven eyes of five patients (50%) at a mean age of 14.14 ± 5.9 years. Six were successfully reattached with mean Snellen best-corrected visual acuity improving from 20/120 preoperatively to 20/60 at last follow-up. Urinalysis in nine patients revealed microhematuria and/or mild proteinuria in six patients (67%). CONCLUSION: LEPREL1 -related high myopia confers a high risk of early-onset GRT-related RRD. The ocular phenotype may be confused with that of ocular Stickler syndrome if genetic testing is not performed. Further investigations into a potential association with renal dysfunction are warranted.

Evolution of macular hole in enhanced S-cone syndrome.

PURPOSE: To describe the stages of development and natural course of a full-thickness macular hole (FTMH) in a patient with enhanced S-cone syndrome (ESCS). METHODS: This study reported the serial ophthalmologic examinations and macular spectral-domain optical coherence tomography (SD-OCT) imaging over a period of 6 years in a 29-year-old man with ESCS confirmed by electroretinography (ERG) and NR2E3 molecular genetic analysis. RESULTS: At presentation, patient had night blindness and visual acuity (VA) of 20/300 in the right eye (OD) and 20/100 in the left eye (OS). Examination showed bilateral retinal midperipheral pigmentary deposits and a macular schisis in OD. Electroretinography and NR2E3 genetic analysis confirmed ESCS. A year later, a lamellar MH (LMH) appeared at the fovea in OD. SD-OCT confirmed it as inner retinal layer LMH with outer retinal preservation and displayed, on the temporal side of the LMH, prominent splitting between the inner and outer retinal layers. At 2 years, a focal defect in the ellipsoid zone appeared on SD-OCT, followed by split in the outer retinal layer creating a progressively expanding outer LMH. The latter had rolled edges which then fused with the inner LMH margins creating a single full-thickness FTMH. Over the next 4 years, enlargement of the FTMH with increased adjacent retinal splitting continued. No visible vitreous abnormalities or vitreoretinal traction forces were identified at any stage during follow-up. VA OD remained unchanged. CONCLUSION: This case illustrates that the clinical evolution of FTMH in ESCS may be progressive and likely involves degeneration and intraretinal, rather than vitreoretinal, traction. This should be kept in mind when considering surgical intervention in these cases.

Late presentation of RPE65 retinopathy in three siblings.

PURPOSE: Gene therapy for RPE65 retinopathy has been recently approved. The purpose of this study was to assess retinal structure and function in 3 siblings presenting with late-stage RPE65 retinopathy and to assess the unmet need for such therapy in Saudi Arabia. METHODS: Search of the retinal dystrophy registry at King Khaled Eye Specialist Hospital and clinical examination including multimodal retinal imaging, full-field electroretinography (ERG), dark adapted full-field stimulus sensitivity thresholds, and molecular genetic testing in 3 patients. RESULTS: Nine (9) patients were identified with biallelic RPE65 mutations, corresponding to a prevalence rate of 9/187 = 5% among early onset retinal dystrophies. Of these, 3 siblings (2 male and 1 female) with RPE65 retinopathy were assessed in detail, because of an unusual, late presentation. They were all over 30 years old at the time of their most recent visits and had non-recordable ERGs. The 2 male siblings presented with poor vision and paracentral loss of the inner segment ellipsoid (ISe) and focal attenuation of the outer nuclear layer (ONL) in the macula. On the other hand, the female sibling presented with 20/100 vision with preserved foveal ISe and intact ONL throughout the macula and significantly lower light sensitivity thresholds compared to her male siblings. A homozygous missense p.Arg91Trp mutation in RPE65 was identified in all. All patients were eligible for gene therapy, demonstrating a central retinal thickness of more than 100 microns on repeated examinations. CONCLUSIONS: RPE65 retinopathy seems to be relatively common on the Arabian peninsula, and in addition it may be underdiagnosed. To the best of our knowledge, this is the first detailed presentation, including multimodal retinal imaging and electrophysiological assessment, of such patients from this region. Patients with late presentation of RPE65 retinopathy may be eligible for gene therapy, in terms of remaining retinal function and structural preservation. The therapeutic window of such therapy remains to be determined.

Analysis of retinal structure and function in cone dystrophy with supernormal rod response.

PURPOSE: To report the clinical and electrophysiological features of cone dystrophy with supernormal rod response (CDSRR). METHODS: Retrospective cohort study of 15 unrelated patients (nine males and six females, median age 16, range 5-47 years) diagnosed with CDSRR by clinical examination, full-field electroretinography (ERG) and genetic testing. OBSERVATIONS: History, ophthalmic examination including near vision, color vision and contrast sensitivity assessment, multimodal retinal imaging and ERG. Genetic testing was done for all patients using next-generation sequencing. RESULTS: The rate of consanguinity was 86.7%. Color vision was defective in 56.3%. Near vision was defective in all patients (mean 20/160). Contrast sensitivity was affected in all patients at low contrast of 2.5%. A parafoveal ring of increased autofluorescence imaging was seen in most patients (75%). Supernormal mixed maximal response b-wave was seen bilaterally in 63% of patients (and high normal in 37%). Rod dysfunction with prolonged rod b-wave latency was detected in all. The 30-Hz flicker response was more reduced and delayed compared to the single-flash cone response. A novel homozygous missense variant c.530G>C (p.Cys177Ser) in KCNV2 was detected in one patient, the nonsense homozygous mutation c.427G>T (p.Glu143*) was found in 13 patients, and the nonsense c.159C>G (p.Tyr53*) was found in one patient. CONCLUSION: This is the largest cohort of CDSRR from a single ethnic background. Rod dysfunction and reduced 30-Hz flicker response were demonstrated in all patients. In contrast to previous descriptions in the literature, a supernormal combined dark-adapted rod-cone ERG was present in the majority of the patients at standard stimulus intensity. Considering the consistent genotype and the demonstration of likely pathogenic genetic variants in all the patients, we argue that the combination of delayed rod b-wave and subnormal flicker response strongly suggests the diagnosis of CDSRR.

Long-term follow-up of retinal function and structure in TRPM1-associated complete congenital stationary night blindness.

Purpose: TRPM1-associated congenital stationary night blindness (CSNB) is characterized by nystagmus and high myopia. We assessed retinal function and structure over long-term follow-up up to 10 years in two siblings from a family with the homozygous deletion c.2394delC in exon 18 that we previously identified. In addition, we describe retinal function and structure in two other siblings with the novel homozygous c.1394T>A (p.Met465Lys) missense mutation. Methods: Clinical examination included full-field electroretinography, axial length measurements, and multimodal retinal imaging. Molecular genetic tests included next-generation sequencing and Sanger sequencing. Results: All patients had non-recordable rod responses and electronegative configuration of the rod-cone responses at presentation. There was a median of 26% reduction in the dark- and light-adapted electroretinographic (ERG) amplitudes over 4 years. Myopia progressed rapidly in childhood but showed only a mild progression after the teenage years. Visual acuities were stable over time, and there was no sign of progressive retinal thinning. All patients had axial myopia. A novel homozygous c.1394T>A (p.Met465Lys) missense mutation in TRPM1 was identified in two siblings. Conclusions: Further prospective study in larger samples is needed to establish whether there is progressive retinal degeneration in TRPM1-associated CSNB. The associated myopia was found to be mainly axial, which has not been described previously. The mechanism of myopia development in this condition remains incompletely understood; however, it may be related to altered retinal dopamine signaling and amacrine cell dysfunction.

Sickle cell retinopathy. A focused review.

PURPOSE: To provide a focused review of sickle cell retinopathy in the light of recent advances in the pathogenesis, multimodal retinal imaging, management of the condition, and migration trends, which may lead to increased prevalence of the condition in the Western world. METHODS: Non-systematic focused literature review. RESULTS: Sickle retinopathy results from aggregation of abnormal hemoglobin in the red blood cells in the retinal microcirculation, leading to reduced deformability of the red blood cells, stagnant blood flow in the retinal precapillary arterioles, thrombosis, and ischemia. This may be precipitated by hypoxia, acidosis, and hyperosmolarity. Sickle retinopathy may result in sight threatening complications, such as paracentral middle maculopathy or sequelae of proliferative retinopathy, such as vitreous hemorrhage and retinal detachment. New imaging modalities, such as wide-field imaging and optical coherence tomography angiography, have revealed the microstructural features of sickle retinopathy, enabling earlier diagnosis. The vascular growth factor ANGPTL-4 has recently been identified as a potential mediator of progression to proliferative retinopathy and may represent a possible therapeutic target. Laser therapy should be considered for proliferative retinopathy in order to prevent visual loss; however, the evidence is not very strong. With recent development of wide-field imaging, targeted laser to ischemic retina may prove to be beneficial. Exact control of intraoperative intraocular pressure, including valved trocar vitrectomy systems, may improve the outcomes of vitreoretinal surgery for complications, such as vitreous hemorrhage and retinal detachment. Stem cell transplantation and gene therapy are potentially curative treatments, which may prevent retinopathy. CONCLUSIONS: There is lack of evidence regarding the optimal management of sickle retinopathy. Further study is needed to determine if recent progress in the understanding of the pathophysiology and diagnosis of sickle retinopathy may translate into improved management and outcome.

Genetic Testing for Wolfram Syndrome Mutations in a Sample of 71 Patients with Hereditary Optic Neuropathy and Negative Genetic Test Results for OPA1/OPA3/LHON.

In this study, the authors present a sample of 71 patients with hereditary optic neuropathy and negative genetic test results for OPA1/OPA3/LHON. All of these patients later underwent genetic testing to rule out WFS. As a result, 53 patients (74.7%) were negative and 18 patients (25.3%) were positive for some type of mutation or variation in the WFS gene. The authors believe that this study is interesting because it shows that a sizeable percentage (25.3%) of patients with hereditary optic 25 neuropathy and negative genetic test results for OPA1/OPA3/LHON had WFS mutations or variants.

Heterozygous mutation in OTX2 associated with early-onset retinal dystrophy with atypical maculopathy.

Purpose: Heterozygous mutations in OTX2 have been associated with a range of ocular and pituitary abnormalities. We report a novel heterozygous deletion in OTX2 underlying early-onset retinal dystrophy with atypical maculopathy. Methods: Clinical examination included electroretinography and multimodal retinal imaging. Molecular genetic testing was composed of next-generation sequencing of a panel of retinal dystrophy genes. Results: A now 17-year-old boy presented 12 years earlier with a history of progressively poor vision since birth, nyctalopia, and early-onset retinal dystrophy with atypical maculopathy. He also had bilateral microphthalmos and a slim prepubertal appearance; growth hormone levels were within normal ranges. Next-generation sequencing of a retinal dystrophy gene panel revealed a heterozygous deletion c.485delC (p.Pro162G.Infs*24) in exon 5 of OTX2. Conclusions: This second report of maculopathy associated with a heterozygous mutation in OTX2 confirms that mutations in OTX2 should be considered in the differential diagnosis of atypical hereditary maculopathy, with or without rod-cone dystrophy.

Teleophthalmology image-based navigated retinal laser therapy for diabetic macular edema: a concept of retinal telephotocoagulation.

BACKGROUND: To determine the feasibility and efficacy of a retinal telephotocoagulation treatment plan for diabetic macular edema. METHODS: Prospective, interventional cohort study at two clinical sites. Sixteen eyes of ten subjects with diabetic macular edema underwent navigated focal laser photocoagulation using a novel teleretinal treatment plan. Clinic 1 (King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia) collected retinal images and fundus fluorescein angiogram. Clinic 2 (Palmetto Retina Center, West Columbia, SC, USA) created image-based treatment plans based on which macular laser photocoagulation was performed back at clinic 1. The primary outcome of the study was feasibility of image transfer and performing navigated laser photocoagulation for subjects with diabetic macular edema between two distant clinics. Secondary measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by spectral-domain optical coherence tomography at 3 months after treatment. RESULTS: The teleretinal treatment plan was able to be successfully completed in all 16 eyes. The mean logMAR BCVA at baseline was 0.49 ± 0.1, which remained stable (0.45 ± 0.1) 3 months after treatment (p = 0.060). The CRT improved from 290.1 ± 37.6 µm at baseline to 270.8 ± 27.7 µm 3 months after treatment (p = 0.005). All eyes demonstrated improvement in the area of retinal edema after laser photocoagulation, and no eyes demonstrated visual acuity loss 3 months after treatment. CONCLUSION: This study introduces the concept of retinal telephotocoagulation for diabetic macular edema, and demonstrates the feasibility and safety of using telemedicine to perform navigated retinal laser treatments regardless of geographical distance.

Three New PAX2 Gene Mutations in Patients with Papillorenal Syndrome.

Papillorenal syndrome (PAPRS; Mendelian Inheritance in Man [MIM] 120330) is an autosomal dominant disease characterised by the presence of congenital renal and optic nerve abnormalities associated with mutations of the PAX2 gene. In this article, the authors present four patients with PAPRS who are carriers of three new PAX2 mutations, as well as another patient with a possible non-pathogenic variant of the PAX2 gene. All patients were given a full neurophthalmological examination, and all patients underwent a genetic test for PAX2. Patients 1 and 2 presented with the classic signs of PAPRS: renal disease associated with a congenitally abnormal optic disc, whereas patients 3 and 4 only presented with a congenital optic nerve abnormality and no renal involvement. In patients 1 and 2, the optic nerves were affected by the presence of a central excavation within the optic disc, absence of the central retinal artery, as well as multiple cilioretinal arteries radiating from the periphery of the optic disc. Bilateral optic nerve pits were seen in patient 3, and lastly, in patient 4 there was the presence of superficial gliotic tissue on the left optic disc. All patients presented with a missense mutation in the PAX2 gene, where in patient 4 possibly being only a non-pathogenic variant of the gene. In conclusion, the authors present two patients with classic clinical signs of PAPRS, having two new PAX2 mutations, which until now have not been described in the current literature; another patient with a new PAX2 mutation showing only ocular manifestations of the disease, and lastly, a patient who is a carrier of a variant of the PAX2 gene has a congenitally abnormal optic disc, which is probably not related to PAPRS.

Congenital stationary night blindness with hypoplastic discs, negative electroretinogram and thinning of the inner nuclear layer.

PURPOSE: To describe congenital stationary night blindness (CSNB) with negative electroretinogram, hypoplastic discs, nystagmus and thinning of the inner nuclear layer (INL). METHODS: Retinal structure was analyzed qualitatively with spectral domain optical coherence tomography and wide field imaging. Retinal function was evaluated with full-field electroretinography (ffERG). Molecular genetic testing included next-generation sequencing (NGS) of the known genes involved in CSNB. RESULTS: Patients presented with CSNB presented with nystagmus, high myopia, hypoplastic discs and negative ffERG with no measurable rod response. The retinas appeared normal and automated segmentation of retinal layers demonstrated a relative reduction of thickness of the INL. There was no significant change in the ffERG after prolonged 2 hour dark adaptation compared to standard 30 minute dark adaptation. Affected family members harboured the homozygous 1-bp deletion c.2394delC in exon 18 of the TRPM1 gene, whereas their unaffected parents were heterozygous carriers. CONCLUSIONS: This data expands the genotype and phenotype spectrum of CSNB. The lack of improvement of rod responses after prolonged dark adaptation, together with thinning of the INL, is compatible with postreceptoral transmission dysfunction in the bipolar cells. Such knowledge may prove useful in future development of treatment for outer retinal dystrophies, using opsin genes to restore light responses in survivor neurons in the inner retina.

Retinal structure in young patients aged 10 years or less with Best vitelliform macular dystrophy.

PURPOSE: Our aim was to analyze retinal structure in young patients with Best disease with reference to future gene therapy. METHODS: This was a retrospective observational spectral domain optical coherence tomography study of four patients aged 10 years or less with Best disease. RESULTS: Findings ranged from subtle thickening at the level of the retinal pigment epithelium-photoreceptor interdigitation line, to subretinal fluid and precipitate-like changes at the level of the photoreceptor outer segments, and further to choroidal neovascularization. The photoreceptor inner segment ellipsoid layer could be visualized seemingly undisturbed above the vitelliform lesions, except in the case of choroidal neovascularization. CONCLUSIONS: Clinical variability is evident even among young patients aged 10 years or less with Best disease. The earliest structural alterations seem to occur at the level of the retinal pigment epithelium-photoreceptor interdigitation line. The photoreceptor inner segment seems to be unaffected unless choroidal neovascularization develops, which seems promising regarding future gene therapy.

Prevalence of Diabetic Retinopathy in a Population of Diabetics From the Middle East With Microvascular Ocular Motor Palsies.

BACKGROUND: Vascular risk factors are increasing rapidly in the Middle East. Growing inactivity and obesity have contributed to an epidemic of Type 2 diabetes mellitus (DM) in the Arab population. Microvascular palsies of the third, fourth, and sixth cranial nerves, which occur in an isolated manner, are relatively common in patients with DM, hypertension, or other vascular risk factors. METHODS: In this retrospective analysis, patients with diabetes with microvascular palsies were assessed for the prevalence of diabetic retinopathy (DR). We compared these data with the prevalence of DR in the general population of diabetics in Saudi Arabia and to a similar published study done in an American population. RESULTS: In total, 126 patients with diabetes were included in the study. The sixth nerve was most frequently involved in 67 patients (53%). Seventy-seven patients (61%) had DR, compared with 49 (39%) without DR. The prevalence of DR in the general population of Saudi patients with diabetes ranged from 30% to 36.1%. CONCLUSIONS: Our study demonstrated a higher prevalence of DR in patients with microvascular palsies compared with the general population of patients with diabetes in the Arab population. This is in contrast to a previous study in an American population. Our results might be secondary to differences between the 2 populations, in particular, the continued increase in the prevalence of vascular risk factors (mainly diabetes) and poor control of these risk factors in the Middle East.

Reappearance of the tapetal-like reflex after prolonged dark adaptation in a female carrier of RPGR ORF15 X-linked retinitis pigmentosa.

PURPOSE: To report changes in the tapetal-like reflex in a female carrier of RPGR ORF15 c.3395delA X-linked retinitis pigmentosa (XLRP) between examinations at 16 and 22 years of age, and to report the observation that the tapetal-like reflex faded due to exposure to daylight and reappeared with prolonged dark adaptation at 22 years of age. METHODS: Clinical examination, kinetic Goldmann perimetry, dark adaptometry, fundus autofluorescence photography, spectral domain optical coherence tomography (SD-OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG) were performed. RESULTS: A female carrier of RPGR XLRP presented with a tapetal-like reflex at age 16. At age 22, the tapetal-like reflex was absent upon examination in daylight; however, the reflex reappeared after 12 h of dark adaptation. Fundus autofluorescence was unremarkable and did not change after prolonged dark adaptation. Full-field electroretinography and dark adaptometry at age 22 demonstrated reduced rod and cone function compared to at age 16. CONCLUSIONS: Dark adaptation before fundus photography may enable the detection of a tapetal-like reflex where it is otherwise invisible. The light-dependent fluctuation of a disease-related substance in the photoreceptors should prompt further study of the potential role of light as a modulator of the progression of RPGR XLRP.

Cone dystrophy associated with autoimmune polyglandular syndrome type 1.

To report the association of autoimmune polyglandular syndrome type 1 (APS1) with cone dystrophy in a large Saudi family. This is a Retrospective chart review and prospective genetic testing and ophthalmic examination of a large multiplex consanguineous family. Genetic testing was performed on 14 family members, seven of whom had detailed ophthalmic examinations. Medical history, ocular history and evaluation, visual field testing, full-field electroretinogram (ERG), and Whole Exome Sequencing (WES) results were analyzed. Three family members were homozygous for c.205_208dupCAGG;p.(Asp70Alafs*148) in AIRE and homozygous for c.481-1G>A in PDE6C. One additional family member was homozygous for only the AIRE variant and another additional family member was homozygous for only the PDE6C variant. All patients with homozygosity for the PDE6C variant had cone dystrophy, and all patients with homozygosity for the AIRE variant had APS1. In addition, two of the family members who were homozygous for the PDE6C and AIRE variants had reduced rod function on ERG. We report the co-inheritance for APS1 and PDE6C-related cone dystrophy, an unusual example of two seemingly independent recessive conditions coinciding within a family. Dual molecular diagnosis must be taken into account by ophthalmologists facing unusual constellations of findings, especially in consanguineous families.

A tapetal-like fundus reflex in a healthy male: evidence against a role in the pathophysiology of retinal degeneration?

PURPOSE: To report on the retinal function and structure in a 37-year-old male who presented with a tapetal-like reflex (TLR) indistinguishable from that seen in female carriers of X-linked retinitis pigmentosa (XLRP). METHODS: Clinical examination included dark adaptometry, full-field electroretinography (ERG), multifocal ERG, optical coherence tomography, and fundus autofluorescence photography. Molecular genetic testing included screening for known mutations in autosomal dominant, autosomal recessive, and X linked retinitis pigmentosa (RP) genes with a commercially available chip, and sequencing analysis of retinitis pigmentosa GTPase regulator (RPGR)-open reading frame 15 (ORF15). RESULTS: Fundus examination revealed a bilateral TLR, which is typical of female carriers of XLRP. Imaging studies and electrophysiological testing was unremarkable, except for a significant increase in full-field ERG amplitudes after prolonged dark adaptation as compared to after standard dark adaptation. Mutation screening was negative. CONCLUSIONS: TLR was found for the first time, to the best of our knowledge, in a male subject. There were no definitive signs of retinal degeneration, suggesting that this reflex in itself is not necessarily a precursor of the retinal degeneration that can be seen in female carriers of XLRP.

Unilateral Retinitis Pigmentosa Associated with Possible Ciliopathy and a Novel Mutation.

Unilateral retinitis pigmentosa (URP) is a rare retinal dystrophy. We describe the clinical course of two patients with (URP) unilateral retinitis pigmentosa confirmed by genetic testing, indicating ciliary dysfunction. Methods: The methods used in this study included a detailed ophthalmic examination, multimodal retinal imaging, Goldmann visual fields, full-field electroretinography (ffERG) and targeted next-generation sequencing. Results: A 32-year-old female (patient 1) and 65-year-old male (patient 2) were found to have URP. ffERG showed a non-recordable response in the affected eye and a response within normal limits in the fellow eye of patient 1, while patient 2 showed non-recordable responses in the apparently unaffected eye and a profound reduction in the photopic and scotopic responses in the affected eye. Next-generation sequencing revealed novel compound heterozygous c.373 C>T (p.Arg125Trp) and c.730-22_730-19dup variants in AGBL5 in patient 1, and a novel hemizygous c.1286 C>T (p.Pro429Leu) in patient 2; both gene mutations were 0%. Segregation analysis was not possible for either of the mutations. Conclusion: This report expands the clinical and molecular genetic spectrum of URP.

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.