Severe retinitis pigmentosa phenotype associated with novel CNGB1 variants.

PURPOSE: To report a severe phenotype of retinitis pigmentosa associated with novel mutations in CNGB1. OBSERVATIONS: Six siblings, age range 50-75 years old, were examined using optical coherence tomography and fundus autofluorescene, electroretinogram testing, Goldman visual field testing, and genetic testing using next generation sequencing.In four affected siblings, two novel compound heterozygous variants in CNGB1 were detected: in exon 26 the missense variant c.2603G > A (p.(Gly868Asp)), and in exon 21, the in-frame 12-bp duplication c.2093_2104dupGCGACCTCATCT (p.(Cys698_lle701dup)). One sibling was unaffected and carried neither of the variants, while another sibling had mild macular degeneration changes and carried the latter variant in heterozygous status. The affected siblings presented with a phenotype showing markedly constricted visual field, flat scotopic and photopic electroretinogram responses and generalized retinal atrophy. CONCLUSIONS AND IMPORTANCE: This is the first report of a 12bp in-frame duplication and a missense variant (in compound heterozygous status) in CNGB1, being associated with a severe form of retinitis pigmentosa featuring extensive peripheral and central retinal degeneration. This study expands the molecular genetic basis of CNGB1-related disease.

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.

DIFFUSE RETINAL VASCULAR LEAKAGE AND CONE-ROD DYSTROPHY IN A FAMILY WITH THE HOMOZYGOUS MISSENSE C.1429G>A (P.GLY477ARG) MUTATION IN CRB1.

PURPOSE: To describe a specific cone-rod dystrophy phenotype in a family with the homozygous c.1429G>A; p.Gly477Arg mutation in CRB1. The detailed phenotype of subjects with this specific mutation has not been described previously. METHODS: Clinical examination included full-field electroretinography and high-resolution and widefield retinal imaging and uveitis workup. Molecular genetic analysis included next-generation sequencing of known retinal dystrophy genes and Sanger sequencing for segregation analysis. RESULTS: Three affected male siblings (26, 16, and 8 years old) were diagnosed with cone-rod dystrophy, featuring bilateral macular hypoautofluorescent lesions. In addition, the eldest brother was found to have retinal vascular leakage throughout the retina without telangiectasia. Uveitis laboratory workup was unremarkable. The homozygous c.1429G>A; p.Gly477Arg mutation in CRB1 was found to segregate with disease in this family. CONCLUSION: To the best of our knowledge, diffuse vascular leakage without telangiectasia or exudation, with bull's eye maculopathy, has not been reported previously in CRB1-cone rod dystrophy. This expands the phenotype complexity associated with CRB1 mutations and confirms that dystrophies associated with mutations in this gene may appear with features of uveitis.

Nd:YAG laser therapy for non-resolving premacular subhyaloid hemorrhage in Saudi patients.

PURPOSE: To report anatomical and visual outcomes of Nd:YAG laser posterior hyaloidotomy (NYPH) in Saudi patients affected by Premacular subhyaloid haemorrhage (PMSHH). METHODS: 8 eyes from 8 patients (7 males and one female) were treated with NYPH when no spontaneous resolution of PMSHH was noticed. The cause of PMSHH was proliferative diabetic retinopathy (PDR) in 3 cases, Central retinal vein occlusion (CRVO) in 2 cases, Valsalva retinopathy in 2 cases, and laser pointer injury in one case. The YAG laser was delivered using a Q switched mode and 3 mirrors contact lens. One attempt of laser delivery was enough in 6 cases and 2 cases needed 2 attempts. The laser power needed ranged between 2 and 4 mJ. RESULTS: Anatomical success was achieved in all cases. The mean LogMAR VA improved from 1.5 before treatment to 0.3 post-treatment. The difference is statistically significant (p = 0.012). No complications related to Nd:YAG laser therapy was reported in any of the study cases until the last follow up. CONCLUSION: To our knowledge, this is the first study to report the outcomes of NYPH for non-resolving PMSHH in Saudi cases. In this small cases series, the procedure seems to be safe, effective, simple, cheap, and non-invasive treatment modality for this disorder that is conducted in the outpatient setting. We think it should be considered as a first option for cases of SHH covering the fovea due to various aetiologies.

Novel causative variants in patients with achromatopsia.

PURPOSE: To report five novel genetic variants in seven unrelated consanguineous families with achromatopsia (ACHM). METHODS: Patients were examined with multimodal retinal imaging and full-field electroretinography (ffERG). Genetic testing was conducted using next-generation sequencing (NGS). RESULTS: Three novel homozygous variants were detected in CNGA3: a missense c.967G > C (p.Ala323Pro) variant was detected in exon 8 (one patient), a splice site variant c.101 + 1G > A in intron 2 (three patients), and a splice site variant c.395 + 1G > T in intron 4(one patient). Another two novel variants were found in PDE6C: a homozygous missense variant c.1899C > A (p.His633Gln) in exon 15 (one patient) and a homozygous splice site variant c.1072-1G > C in intron 7 (one patient). Mutation segregation assessment was possible in 3 of the 7 families. All patients had nonrecordable ffERG 30-Hz flicker responses, reduced single-flash cone responses but preserved rod responses. Patients presented with variable degrees of foveal outer retinal layer loss and variable patterns of foveal hyperautofluorescence. CONCLUSIONS: These novel variants expand the genotypes associated with ACHM and may help in future therapy development for ACHM.

Severe retinal degeneration at an early age in Usher syndrome type 1B associated with homozygous splice site mutations in MYO7A gene.

PURPOSE: Usher syndrome is the most common cause of deafness associated with visual loss of a genetic origin. The purpose of this paper is to report very severe phenotypic features of type 1B Usher syndrome in a Saudi family affected by positive homozygous splice site mutation in MYO7A gene. METHODS: Affected siblings went through detailed history. Complete ophthalmic examination was done. Imaging with colour fundus photography, fundus autofluorescence (AF), and optical coherence tomography (OCT) scans was performed. Full field electroretinogram (ffERG) was recorded. Molecular genetic testing was done using next-generation sequencing. RESULTS: Visual acuity was more reduced (range 20/300-20/40) in older siblings (age>30 years), than in younger (age <30 years) siblings (range 20/70-20/25). OCT scans showed macular atrophy in all but one case that has cystoid macular edema (CME). AF demonstrated atrophy outside a small foveal area showing high signal. FfERG was flat in all cases. The homozygous splice site mutation c.470+1G>A in intron 5 of the MYO7A gene was detected in all affected siblings. CONCLUSIONS: This mutation manifested with advanced retinal degeneration at a young age. This may have implications regarding future gene therapy in Usher syndrome cases with this genotype.

Serous retinal detachment after panretinal photocoagulation for proliferative diabetic retinopathy: a case report.

BACKGROUND: Proliferative diabetic retinopathy is a major cause of visual impairment in working-age adults worldwide. Panretinal photocoagulation is a cornerstone in its management; however, it may include a range of side effects and complications, one of these being serous retinal detachment. To the best of our knowledge, this is the first report of the use of intravitreal injection of bevacizumab for serous retinal detachment after panretinal photocoagulation. CASE PRESENTATION: A 24-year-old Saudi man with poorly controlled type 1 diabetes presented with bilateral progressive proliferative retinopathy in spite of several sessions of panretinal photocoagulation. After one additional such session, he developed bilateral serous retinal detachment and vision loss, which was managed with a single bilateral intravitreal bevacizumab injection. The serous retinal detachment subsided with partial recovery of vision. CONCLUSIONS: Serous retinal detachment after panretinal photocoagulation for proliferative diabetic retinopathy is a rare complication nowadays. In this case, it seems that excessive photocoagulation exceeded the energy-absorbing capacity of the retinal pigment epithelium, leading to a disruption of the blood-retinal barrier. A single injection of bilateral intravitreal bevacizumab was sufficient to control the serous retinal detachment. This effect may have been due to a reduction of vascular leakage resulting from the mechanism of action of this drug. No complications were noted from the injection. Caution should be exerted when attempting bilateral panretinal photocoagulation.

A Case of Unilateral Retinitis Pigmentosa Associated with Full Thickness Macular Hole.

A 44-year-old Saudi female presented with poor right eye vision for 3 years. Visual acuity (VA) was 20/400 in the right eye and 20/20 in the left eye. Examination and imaging showed all the typical features of retinitis pigmentosa in the right eye associated with full thickness macular hole (FTMH) and an essentially normal left eye. The case underwent pars plana vitrectomy with internal limiting membrane peeling and gas tamponade that resulted in anatomical closure of the FTMH, but VA remained the same.

Pneumatic displacement of submacular haemorrhage.

PURPOSE: To evaluate the outcomes of pneumatic displacement of submacular hemorrhage secondary to choroidal neovascular membrane (CNV) (n = 9) and retinal arterial macroaneurysm (RAM) (n = 3). METHODS: This is a retrospective case series study of 12 eyes from 12 patients in Aberdeen Royal Infirmary, Aberdeen, UK. The mean duration of visual loss was 10.8 ± 4.11 days. All cases received intravitreal injection of expansile gas within 24 h of presentation (C3F8 in 11 cases and SF6 in one case) and postured face down for five days. Anterior chamber paracentesis was done right after gas injection. Intravitreal anti-VEGF was injected at the same time in cases with CNV. Further anti-VEGF injections were done in CNV cases as needed afterwards. Cases were followed up for 6 months. RESULTS: The submacular hemorrhage was successfully displaced from underneath the fovea in all but one case. The bleeding disappeared totally in 44% of cases and was inferiorly displaced in 56%. VA improvement at 6 months was statistically significantly higher than baseline VA. All cases but 2 (one because of subfoveal fibrosis and one because of late presentation) experienced improved VA. The mean VA improved from 1.37 ± 0.18 logMAR at baseline to 0.83 ± 0.26 logMAR at 6 months. No complication related to the procedure was reported. CONCLUSION: Pneumatic displacement of submacular hemorrhage appears to be a safe and effective technique to treat the condition. It is an easy procedure that can be done in outpatient setting. Further studies are needed to validate our results.

Accidental macular injury with class IVb laser outside the medical settings.

In the medical settings, safety precautions are used to mitigate inadvertent ocular damage due to laser beams. High power lasers are illegal in many countries; however, they are sometimes used on social occasions. Use by an untrained member of the public can result in severe accidental ocular damage. We report a case of macular damage and central visual loss due to the illegal use of a class IVb 2000 mW power laser in a 20-year-old male. To our knowledge, this is the first case of macular injury due to this particular type of laser. The case history and management over a 6-month period is described. Pubic education initiatives are required to increase the awareness of the dangerous nature of laser beam exposure outside a medical setting.

Retinal pigment epithelial atrophy in patients with exudative age-related macular degeneration undergoing anti-vascular endothelial growth factor therapy.

PURPOSE: To evaluate the occurrence of retinal pigment epithelial atrophy in patients with age-related macular degeneration undergoing anti-vascular endothelial growth factor therapy. METHODS: The study is a retrospective review. Eligible were patients with age-related macular degeneration and choroidal neovascular membranes treated with anti-vascular endothelial growth factor between October 2007 and February 2011; they were followed for >3 months, with fundus photographs and fluorescein angiography at baseline and with autofluorescence and near-infrared autofluorescence images at baseline and follow-up. Demographics, visual acuity, the type of choroidal neovascular membranes, the number of treatments performed, and the length of follow-up were recorded. Autofluorescence and near-infrared autofluorescence images were evaluated for the presence or absence of areas of reduced signal. A multilevel logistic regression model was used to investigate the factors that may be associated with "progression of atrophy" at follow-up, which was the primary outcome of this study. RESULTS: Sixty-three patients (72 eyes) were followed for a median of 16 months (range, 3-36 months). Atrophy at baseline was observed in 47% (34/72) of eyes; progression of atrophy occurred in 62% (45/72) of eyes at the last visit. The number of anti-vascular endothelial growth factor injections received was statistically significantly associated with the progression of atrophy at follow-up (odds ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02). CONCLUSION: Atrophy was frequently observed in patients with age-related macular degeneration and choroidal neovascular membranes undergoing anti-vascular endothelial growth factor therapy.

Heavier-than-water silicone oil mixture as a long-term tamponade agent: a pilot study.

PURPOSE: To evaluate the tamponade effect on the retina of a heavier-than-water silicone oil mixture and to compare it with the effect of silicone oil. METHODS: Prospective, non-randomised, comparative pilot study. Phakic/pseudophakic patients with retinal detachment undergoing vitrectomy with Densiron 68 or silicone oil were recruited. The 'separation volume', defined as the relative volume of the space between intraocular tamponade agent and retina, was estimated using magnetic resonance imaging in both groups and compared. RESULTS: Nine participants were included; 4 received silicone oil and 5 Densiron 68. The mean separation volume was statistically significantly larger in the silicone oil group (0.477 ± 0.419 cm(3)) than in the Densiron group (0.042 ± 0.013 cm(3); p = 0.014). CONCLUSIONS: In this study Densiron achieved an excellent tamponade effect in the retina.

In vivo safety of trypan blue use in vitreoretinal surgery.

PURPOSE: The purpose of this study was to evaluate "in vivo" safety of trypan blue (TB) in patients undergoing TB-assisted internal limiting membrane or epiretinal membrane peeling. METHODS: Prospective study including 21 patients (21 eyes) with full-thickness macular hole and/or epiretinal membrane undergoing TB-assisted internal limiting membrane/epiretinal membrane peeling. Main outcome measures included distance visual acuity, near visual acuity, amplitude of P50 and N95 of the pattern electroretinogram, and fundus autofluorescence; these were assessed preoperatively, at 6 months (n = 21) and 12 months (n = 10) postoperatively. RESULTS: There was a statistically significant improvement in distance visual acuity, near visual acuity, P50, and N95 amplitude at 6 months and 12 months postoperatively. The mean logarithm of the minimum angle of resolution distance visual acuity and near visual acuity improved from baseline by 0.31 (SD 0.37) and 0.17 (SD 0.31) at 6 months, respectively, and by 0.4 (SD 0.25) and 0.35 (SD 0.28) at 12 months, respectively. The mean P50 and N95 component amplitudes improved by 28% compared with baseline at 6 months (P50 0.4 [SD 0.8]; N95 0.53 [SD 1.07]) and by 63% at 12 months (P50 0.9 [0.85]; N95 1.04 [1.34]). Autofluorescence did not demonstrate damage to the retinal pigment epithelium attributable to TB. CONCLUSION: No deleterious effects of TB were observed in this study.

Internal limiting membrane peeling in vitreo-retinal surgery.

Peeling the internal limiting membrane of the retina has become a very common procedure performed by vitreo-retinal surgeons. The combination of new microsurgical instrumentation with the availability of different dyes to stain this thin and transparent membrane has facilitated the performance of internal limiting membrane peeling, reducing the time and trauma associated with this maneuver. Internal limiting membrane peeling has been used to treat a variety of retinal pathologies, including full-thickness macular hole, epiretinal membrane, macular edema, vitreomacular traction syndrome, and Terson syndrome, among others. Although it appears that peeling the internal limiting membrane in these retinal conditions may be associated with better anatomical and visual outcomes following surgery, further evidence through randomized controlled clinical trials is still needed to guide the vitreo-retinal surgeon on the appropriate use of this surgical maneuver.