Vitreoretinal Degeneration Research Articles

Wagner Syndrome-like fundus presentation of atypical Persistent Fetal Vasculature.

To report the case of a woman with atypical Persistent fetal vasculature (PFV) accompanied by more typical findings of Wagner Syndrome. A 58-year-old woman complained about persistent flashes and floaters for more than 6 months. Multimodal retinal imaging showed Bergmeister papilla and a fibrous gray strand floating behind the macula in the right eye. Ultra-wide field retinography revealed a 270° paving-stone degeneration and a nasal circumferential vitreous veil in both eyes. Functional and genetic testing were negative for inherited retinal diseases. PFV spectrum confirms its heterogeneous presentation. We report an atypical adult PFV case in presence of retrolental and optic nerve head stalks, accompanied by extensive peripheral vitreoretinal degenerations. This case may expand the current understanding of PFV presentation in adulthood.

Exploring Knobloch syndrome: A case series of two Indian families and a review of literature

This case series describes the clinical features and genetic testing results of four patients from two families affected by Knobloch syndrome (KS). KS is an autosomal recessive collagenopathy characterized by vitreoretinal degeneration, high myopia, retinal detachment, and occipital encephalocele. In addition, a myriad of other ophthalmic and systemic features may be present in the affected individuals. Mutations in the COL18A1 gene are primarily implicated in the pathogenesis of the disease. The phenotypical differences seen in our genetically-proven patients show the clinical heterogeneity of this condition. Diagnosis of KS type-1 was confirmed by genetic analysis in all affected patients. Surgical intervention was done to salvage vision in three patients. This case series highlights the importance of meticulous clinical examination and diagnosis of this rare condition. Genetic counseling and testing are important for suspected patients and for guiding patients on the visual prognosis of the disease.

Nonperfusion of the Far Peripheral Retina in Highly Myopic Stickler Syndrome.

Purpose: To describe the clinical course of 3 patients with Stickler syndrome found on fluorescein angiography (FA) to have nonperfusion of the peripheral retina. Methods: Three patients with confirmed Stickler syndrome were examined under anesthesia. Genetic testing and FA were performed. Results: Each patient had characteristic ocular findings of Stickler syndrome, including high myopia with vitreoretinal degeneration. FA was performed on each patient and showed 360 degrees of nonperfusion of the retinal periphery in all eyes, with mild leakage in Case 3. Conclusions: The current series presents evidence of peripheral retinal nonperfusion in 3 consecutive patients with Stickler syndrome. Based on these findings, the authors recommend adopting FA as a standard imaging modality and using laser photocoagulation to treat the areas of retinal nonperfusion for all patients with Stickler syndrome.

Our experience of surgical treatment of peripheral retinoschisis without capturing the macular zone using scleral buckling

Purpose: to present our experience of surgical treatment of peripheral retinoschisis without macular involvement using a scleral buckle.Material and methods. 31 patients (31 eyes) with peripheral retinoschisis (PR) without macular involvement, including 19 cases complicated by retinal detachment, underwent scleral buckling with cryoretinopexy of rupture zones and vitreoretinal degeneration and transscleral drainage of subretinal fluid.Results. In 12 (39 %) cases, the retina reattached within 24 hours after the operation, in 11 (35 %) cases, it reattached within 1 week, while in 8 (26 %) cases complete resorption of the subretinal fluid and retinal reattachment occurred 1 to 6 months after the operation. By the end of the 6-month follow-up period, retinal reattachment was achieved in all cases.Conclusion. The surgical treatment tactics of PR without macular involvement by scleral buckling is effective and pathogenetically validated, especially in the case of progressing lretinoschisis.

Vitreoretinopathy-Associated Pediatric Retinal Detachment Treatment Outcomes: IRIS® Registry (Intelligent Research in Sight) Analysis.

To determine the treatment patterns and outcomes of pediatric retinal detachments (RDs) associated with hereditary vitreoretinopathies. Retrospective cohort analysis using IRIS® Registry (Intelligent Research in Sight) database. Patients < 18 years old with a rhegmatogenous RD and a systemic disorder associated with vitreoretinal degeneration (e.g., Stickler syndrome) or other malformation of the vitreous from 2013-2019. Cases were identified using International Classification of Diseases, Ninth and Tenth Revisions (ICD-9, ICD-10) diagnostic codes from the IRIS® Registry cohort. Other hereditary vitreoretinopathies that are not encoded by specific ICD code(s) were captured by text search. Nonspecific vitreous abnormality ICD codes were also included. Exclusion criteria included traumatic retinal detachments using ICD codes for ocular trauma and serous or exudative retinal detachment. Surgical procedures were identified using Current Procedural Terminology (CPT) codes for repair of retinal detachment. Baseline demographic information collected included age, gender, race/ethnicity, geographic region of the provider location, and health insurance status. Main outcomes measured in this study were average time to first surgery, number of eyes presenting with bilateral detachments, and choice of initial surgical procedure. A total of 2115 eyes of 1722 patients were identified (mean age, 10.4 years; 58% male). The median time to first surgery was 7 days (interquartile range, 40 days). One thousand four hundred seven eyes of 1134 patients had ≥ 1 year of follow-up, with 506 eyes (36%) developing a fellow eye RD. Thirty-three percent of patients presenting with bilateral detachments, and 349 eyes had initial RD surgery within 1 year of the index date documented by CPT code. Fellow eye detachment occurred a mean of 32 days after initial presentation. The mean number of surgeries per eye within 1 year was 1.68. Best-corrected visual acuity did not improve from a baseline 20/54 to 20/62. The initial procedure was most commonly complex RD repair (n = 176), followed by scleral buckle (n = 102), pars plana vitrectomy (n = 89), laser (n = 59), cryotherapy (n = 5), and pneumatic retinopexy (n = 5). There were 51 new diagnoses of glaucoma and 37 new diagnoses of aphakia within 1 year after the surgical procedure. IRIS Registry data provide insight into rare pediatric vitreoretinopathy-associated RDs, which have a high rate of reoperation and fellow eye involvement. Proprietary or commercial disclosure may be found after the references.

“White without Pressure” Associated with Other Degenerations: Features of Vitreoretinal Interface on OCT Scans (Clinical Case)

“White without pressure” warrants special attention from ophthalmologists due to the lack of consensus on its etiopathogenesis and associated risk of rhegmatogenous retinal detachment. “White without pressure” appears in various quadrants of the fundus as an area white to gray in color. It is more common in persons with high myopia.The paper presents a clinical case of a 19-year-old male with an association between “white without pressure”, “dark without pressure”, vitreoretinal tuft and symptomatic floaters in the left eye. OCT scanning (SOLIX) was employed to assess the vitreoretinal interface. OCT revealed the intraretinal location of “white without pressure” and “dark without pressure” degenerations without vitreoretinal traction. “White without pressure” degeneration is hyperreflective at the level of the outer retina in the photoreceptor ellipsoid and myoid zones, and “dark without pressure” is hyporeflective at this level. Vitreoretinal tuft is a vitreoretinal degeneration located at the level of the inner limiting membrane. It was detected as a hyperreflective site with vitreoretinal adhesion leading to traction and thickening of the corresponding retinal area. The combination of the three degenerations poses a risk of rhegmatogenous retinal detachment due to the presence of the vitreoretinal tuft.

The unique structural characteristics of the Kir 7.1 inward rectifier potassium channel: a novel player in energy homeostasis control.

The inward rectifier potassium channel Kir7.1, encoded by the KCNJ13 gene, is a tetramer composed of two-transmembrane domain-spanning monomers, closer in homology to Kir channels associated with potassium transport such as Kir1.1, 1.2, and 1.3. Compared with other channels, Kir7.1 exhibits small unitary conductance and low dependence on external potassium. Kir7.1 channels also show a phosphatidylinositol 4,5-bisphosphate (PIP2) dependence for opening. Accordingly, retinopathy-associated Kir7.1 mutations mapped at the binding site for PIP2 resulted in channel gating defects leading to channelopathies such as snowflake vitreoretinal degeneration and Leber congenital amaurosis in blind patients. Lately, this channel's role in energy homeostasis was reported due to the direct interaction with the melanocortin type 4 receptor (MC4R) in the hypothalamus. As this channel seems to play a multipronged role in potassium homeostasis and neuronal excitability, we will discuss what is predicted from a structural viewpoint and its possible implications for hunger control.

Retinal Development and Pathophysiology in Kcnj13 Knockout Mice.

Purpose: We constructed and characterized knockout and conditional knockout mice for KCNJ13, encoding the inwardly rectifying K+ channel of the Kir superfamily Kir7.1, mutations in which cause both Snowflake Vitreoretinal Degeneration (SVD) and Retinitis pigmentosa (RP) to further elucidate the pathology of this disease and to develop a potential model system for gene therapy trials. Methods: A Kcnj13 knockout mouse line was constructed by inserting a gene trap cassette expressing beta-galactosidase flanked by FRT sites in intron 1 with LoxP sites flanking exon two and converted to a conditional knockout by FLP recombination followed by crossing with C57BL/6J mice having Cre driven by the VMD2 promoter. Lentiviral replacement of Kcnj13 was driven by the EF1a or VMD2 promoters. Results: Blue-Gal expression is evident in E12.5 brain ventricular choroid plexus, lens, neural retina layer, and anterior RPE. In the adult eye expression is seen in the ciliary body, RPE and choroid. Adult conditional Kcnj13 ko mice show loss of photoreceptors in the outer nuclear layer, inner nuclear layer thinning with loss of bipolar cells, and thinning and disruption of the outer plexiform layer, correlating with Cre expression in the overlying RPE which, although preserved, shows morphological disruption. Fundoscopy and OCT show signs of retinal degeneration consistent with the histology, and photopic and scotopic ERGs are decreased in amplitude or extinguished. Lentiviral based replacement of Kcnj13 resulted in increased ERG c- but not a- or b- wave amplitudes. Conclusion: Ocular KCNJ13 expression starts in the choroid, lens, ciliary body, and anterior retina, while later expression centers on the RPE with no/lower expression in the neuroretina. Although KCNJ13 expression is not required for survival of the RPE, it is necessary for RPE maintenance of the photoreceptors, and loss of the photoreceptor, outer plexiform, and outer nuclear layers occur in adult KCNJ13 cKO mice, concomitant with decreased amplitude and eventual extinguishing of the ERG and signs of retinitis pigmentosa on fundoscopy and OCT. Kcnj13 replacement resulting in recovery of the ERG c- but not a- and b-waves is consistent with the degree of photoreceptor degeneration seen on histology.

Spontaneous Resolution of a Rhegmatogenous Retinal Detachment

Abstract A retinal detachment is the term used to describe detachment of the neurosensory retina from the underlying membrane, the retinal pigment epithelium (RPE). Rhegmatogenous detachments are caused by a break in the retina through which fluid passes from the vitreous cavity into the subretinal space. The incidence of rhegmatogenous retinal detachment in the general population in Europe is 1 in 10 000 persons per year. Danger is the greatest in the age range from 55 to 70 years. Without treatment, blindness in the affected eye may occur. Individual risks depend on the presence or absence of specific factors including myopia, positive family anamnesis, retina rupture, trauma, ablation in the other eye, ablation in a vitreous body, retina high-risk peripheral de-generations and vitreoretinal degenerations. Majority of the untreated rhegmatogenous retina ablations progress to the subtotal or total retinal detachment and blindness. This paper describes a very rare case of the spontaneous complete reattachment of the sensory retina to the retinal pigment epithelium in a patient with the total rhegmatogenous retinal ablation in the right eye. The female patient, who was 52 years old, was examined by an Ophthalmologist after she had experienced a sudden loss of vision, 2 months before appointment. After a detailed ophthalmological examination, a total rhegmatogenous retinal ablation of the right eye was diagnosed. The best corrected visual acuity, evaluated on a Snellen chart, was 2/60. The patient was referred to a tertiary-level Institution since a surgical intervention of the ablation was needed. Due to technical inabilities in the above-mentioned Institution, the operation was not performed, and despite the recommendation to perform the intervention in another tertiary level Institution, the patient did not have ophthalmological examinations during the following three months. During the next visit, the Ophthalmologist determined that there was a spontaneous retinal fixation on the retinal pigment epithelium and a partial restoration of the visual function of the affected eye which was evaluated at 0.5.

Late ophthalmology findings in a X-linked juvenile retinoschisis patient

X-linked juvenile retinoschisis (XLRS) is a vitreoretinal degeneration caused by mutations in the RS1 gene, generally characterized by bilateral maculopathy and peripheral retinoschisis leading to progressive visual loss during the first 2 decades of life and complications like retinal detachment and vitreous hemorrhage. Herein, we present late ophthalmology findings in a XLRS patient. Late ophthalmology findings in a X-linked juvenile retinoschisis patient

Goldmann favre syndrome: A rare case report

Goldmann Favre syndrome (GFS) is a vitreotapetoretinal degeneration also called as Favre microfibrillar vitreoretinal degeneration. We report the case of a 24-year-old male who presented with defective vision in both eyes for 10 years with a history of defective night vision. He was diagnosed with GFS, by fundus examination and electroretinogram. He was treated with low vision aids.

Knobloch Syndrome in Siblings with Posterior Fossa Malformations Along with Cerebellar Midline Cleft Abnormality Caused by Biallelic COL18A1 Mutation: Case-Based Review.

Knobloch syndrome (KS) is an autosomal recessive disorder caused by biallelic pathogenic variants in COL18A1 . KS clinically manifests with the typical eye findings (high myopia, vitreoretinal degeneration, retinal detachment, and lens subluxation), variable neurological findings (occipital encephalocele, polymicrogyria, cerebellar malformations, epilepsy, and intellectual disability), and the other uncommon clinical manifestations. Literature review of all KS patients (source PubMed) was done with special reference to cerebellar abnormalities. Here, we report two siblings with typical KS with posterior fossa malformations and novel cerebellar midline cleft abnormality analyzed by whole exome sequencing. Known pathogenic homozygous variant c.2908C > T; (p.Arg970Ter) in exon 26 of COL18A1 was found as a cause for KS. These two siblings presented with early-onset severe ocular manifestations, facial dysmorphism, and variable central nervous system manifestations along with novel cerebellar midline cleft abnormality. The presence or absence of structural brain malformations and genotypes does not absolutely predict cognitive functions in KS patients. However, the presence of posterior fossa abnormality may be predictive for the development of ataxia in later life and needs further studies.

Altered phosphatidylinositol regulation of mutant inwardly rectifying K+ Kir7.1 channels associated with inherited retinal degeneration disease.

Kir7.1 K+ channel expressed in retinal pigment epithelium is mutated in inherited retinal degeneration diseases. We study Kir7.1 in heterologous expression to test the hypothesis that pathological R162 mutation to neutral amino acids results in loss of a crucial site that binds PI(4,5)P2 . Although R162W mutation inactivates Kir7.1, changes to smaller volume (e.g. Gln) amino acids are tolerated or even enhance function (Ala or Cys). Chemical modification of Kir7.1-R162C confirms that large residues of the size of Trp are incompatible with normal channel function even if positively charged. In addition to R162, K164 (and possibly K159) forms a binding site for the phosphoinositide and is essential for channel activity. R162 substitution with a large, neutral side chain like Trp exerts a dominant negative effect on Kir7.1 activity such that less than one fifth of the full activity is expected in a cell expressing the same amount of mutant and wild-type channels. Mutations in the Kir7.1 K+ channel, highly expressed in retinal pigment epithelium, have been linked to inherited retinal degeneration diseases. Examples are mutations changing Arg 162 to Trp in snowflake vitreoretinal degeneration (SVD) and Gln in retinitis pigmentosa. R162 is believed to be part of a site that binds PI(4,5)P2 and stabilises the open state. We have tested the hypothesis that R162 mutation to neutral amino acids will result in the loss of this crucial interaction to the detriment of channel function. Our findings indicate that although R612W mutation inactivates Kir7.1, changes to smaller volume (e.g. Gln) amino acids are tolerated or even enhance function (Ala or Cys). Cys chemical modification of Kir7.1-R162C confirms that large residues of the size of Trp are incompatible with normal channel function even if positively charged. Experiments titrating the levels of plasma membrane PI(4,5)P2 with voltage-dependent phosphatase DrVSP reveal that, in addition to R162, K164 (and possibly K159) forms a binding site for the phosphoinositide and ensures channel activity. Finally, the use of a concatemeric approach shows that substitution of R162 with a large, neutral side chain mimicking a Trp residue exerts a dominant negative effect on Kir7.1 activity such that less than one fifth of the full activity is expected in heterozygous cells carrying the SVD mutation. Our results suggest that if mutations in the human KCNJ13 gene resulting in the neutralisation of R162 and Kir7.1 malfunction led to retinal degeneration diseases, their severity might depend on the nature of the side chain of the replacing amino acid.

X-linked Retinoschisis Discovered after Congenital Cataract Surgery

X-linked retinoschisis (XLRS) is a rare, hereditary, and bilateral vitreoretinal degeneration, associating maculopathy and vitreoretinopathy. We report the case of X-linked retinoschisis diagnosed after congenital cataract surgery in a child.

Radiologic Features of Type II and Type XI Collagenopathies.

Type II collagen is a major component of the cartilage matrix. Pathogenic variants (ie, disease-causing aberrations) in the type II collagen gene (COL2A1) lead to an abnormal structure of type II collagen, causing a large group of skeletal dysplasias termed type II collagenopathies. Because type II collagen is also located in the vitreous body of the eyes and inner ears, type II collagenopathies are commonly associated with vitreoretinal degeneration and hearing impairment. Type II collagenopathies can be radiologically divided into two major groups: the spondyloepiphyseal dysplasia congenita (SEDC) group and the Kniest-Stickler group. The SEDC group is characterized by delayed ossification of the juxtatruncal bones, including pear-shaped vertebrae. These collagenopathies comprise achondrogenesis type 2, hypochondrogenesis, SEDC, and other uncommon subtypes. The Kniest-Stickler group is characterized by disordered tubular bone growth that leads to "dumbbell" deformities. It comprises Kniest dysplasia and Stickler dysplasia type 1, whose radiographic manifestations overlap with those of type XI collagenopathies (a group of disorders due to abnormal type XI collagen) such as Stickler dysplasia types 2 and 3. This phenotypic overlap is caused by type II and type XI collagen molecules sharing part of the same connective tissues. The authors describe the diagnostic pathways to type II and type XI collagenopathies and the associated differential diagnoses. In addition, they review the clinical features and genetic bases of these conditions, which radiologists should know to participate in multidisciplinary care and translational research. Online supplemental material is available for this article. ©RSNA, 2020.

Macular Hole–Related Retinal Detachment in Children with Knobloch Syndrome

To describe the findings and the management of macular hole (MH)-related retinal detachment (RD) in children with Knobloch syndrome. Retrospective interventional case series. Patients with Knobloch syndrome who presented with MH-related RD. Retrospective chart review of patients with Knobloch syndrome who presented with MH-related RD from January 2012 to December 2018. Interventions included pars plana vitrectomy and silicone oil tamponade with or without scleral buckle, drainage retinotomy, or relaxing retinectomy. MH characteristics and surgical anatomical outcome. The study included 9 eyes of 5 patients (age range 2 months to 5 years; median age 5.5 months). Presenting symptoms were poor fixation and nystagmus. The fellow eye of 1 patient had RD due to peripheral breaks. The MH was clinically visible in 8 eyes and detected only by OCT in 1 eye. The RD was shallow and extended to the anterior equator in 7 eyes and localized to a punched-out atrophic lesion in 1 eye. Seven eyes underwent surgical repair. At the last follow-up examination (follow-up range 11 to 42 months; mean 24 months, standard deviation 11.8 months), retinal reattachment with MH closure was achieved in 5 eyes along with marked improvement in fixation. Patients with Knobloch syndrome may develop MH-related RD as early as infancy. The condition may be easily overlooked in children but should be suspected in the setting of high myopia, vitreoretinal degeneration, and encephalocele.

Missense variants in the conserved transmembrane M2 protein domain of KCNJ13 associated with retinovascular changes in humans and zebrafish

Mutations in KCNJ13 are associated with two retinal disorders; Leber congenital amaurosis (LCA) and snowflake vitreoretinal degeneration (SVD). We describe a novel fibrovascular proliferation in the retina of two affected members of a KCNJ13-related LCA family with a homozygous c.458C > T, p.(Thr153Ile) missense mutation. Optical coherence tomography retinal imaging of the kcnj13 mutant zebrafish (obelixtd15 c.502T > C, p.[Phe168Leu]) revealed a late onset retinal degeneration at 12 months, with retinal thinning and associated retinovascular changes, including increased vessel calibre and vitreous deposits. Both human and zebrafish variants are missense and located within the conserved transmembrane M2 protein domain, suggesting that disruption of this region may contribute to retinovascular changes as an additional feature to the previously described LCA phenotype. Close monitoring of other patients with similar mutations may be required to minimise the ensuing retinal damage.

Rhegmatogenous Retinal Detachment in Nonsyndromic High Myopia Associated with Recessive Mutations in LRPAP1

To describe a new form of childhood-onset rhegmatogenous retinal detachment (RRD) in autosomal recessive high myopia associated with mutations in LRPAP1. Retrospective cohort study. A total of 12 children (24 eyes) with recessive LRPAP1 mutations and associated high myopia. Serial ophthalmological examination and retinal imaging during 4.6±1.9 (mean ± standard deviation) years. Retinal interventions included prophylactic laser and surgical retinal repair. Incidence and recurrence rate of RRD and retinal break formation. Association between LRPAP1 genotypes and RRD characteristics. Some 42% of children (5 children [6 eyes]) developed RRD at the age of 10.43±0.97 years. Four of the children who developed RRD were male (80%), and 1 was female (20%). Visual acuity was significantly reduced in eyes with RRD at presentation and at the most recent visit compared with eyes with no RRD (P < 0.001 for both). Two eyes had inoperable RRD. Four eyes for which primary retinal repair was done had redetachment (100% of operated eyes) due to variable degrees of proliferative vitreoretinopathy (PVR). Reattachment after surgical repair, which was maintained at least during 6 months of follow-up, was achieved in 3 eyes (75%), with final visual acuities of 20/300 in 2 eyes and 20/400 in 1 eye. This is the first description of a nonsyndromic, high myopia-related, recessive RRD without any signs of vitreoretinal degeneration. Recessive LRPAP1 gene mutations confer a high risk of childhood-onset RRD and PVR. Proliferative vitreoretinopathy in turn increases the risk of recurrent RRD and may lead to blindness. Recognizing the LRPAP1-related high myopia phenotype is important, and early childhood examination with additional close follow-up and prophylactic retinal laser should be considered.

Optical Coherence Tomography in Knobloch Syndrome.

Knobloch syndrome is a genetic disorder defined by occipital defect, high myopia, and vitreoretinal degeneration. The authors studied retinal changes in patients with Knobloch syndrome using optical coherence tomography (OCT). The authors report patients with Knobloch syndrome who received OCT testing during their care from 2011 to 2016. Diagnosis was based on high myopia, characteristic fundus, and occipital scalp or skull abnormalities with/without featureless irides and/or ectopia lentis. When available, diagnosis was confirmed by the detection of COL18A1 mutations. The authors studied eight eyes from five patients. Two eyes were excluded due to chronic retinal detachment. OCT findings included epiretinal membrane, peripapillary vitreoretinal traction with retinoschisis, absent or rudimentary foveal pits, mean macular thickness of 113.4 μm, poor lamination, retinal pigment epithelium (RPE) atrophy, photoreceptor depletion, and mean choroidal thickness of 168.5 μm with enlarged choroidal vessels. OCT findings in Knobloch syndrome include abnormal vitreoretinal traction, poor foveal differentiation, poor retinal lamination, retinal thinning, RPE attenuation, myopic choroidal thinning, and pachychoroid. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e203-e210.].

Phagosomal and mitochondrial alterations in RPE may contribute to KCNJ13 retinopathy

Mutations in KCNJ13 are associated with two retinal disorders; Leber congenital amaurosis (LCA) and snowflake vitreoretinal degeneration (SVD). We examined the retina of kcnj13 mutant zebrafish (obelixtd15, c.502T > C p.[Phe168Leu]) to provide new insights into the pathophysiology underlying these conditions. Detailed phenotyping of obelixtd15 fish revealed a late onset retinal degeneration at 12 months. Electron microscopy of the obelixtd15 retinal pigment epithelium (RPE) uncovered reduced phagosome clearance and increased mitochondrial number and size prior any signs of retinal degeneration. Melanosome distribution was also affected in dark-adapted 12-month obelixtd15 fish. At 6 and 12 months, ATP levels were found to be reduced along with increased expression of glial fibrillary acidic protein and heat shock protein 60. Quantitative RT-PCR of polg2, fis1, opa1, sod1/2 and bcl2a from isolated retina showed expression changes consistent with altered mitochondrial activity and retinal stress. We propose that the retinal disease in this model is primarily a failure of phagosome physiology with a secondary mitochondrial dysfunction. Our findings suggest that alterations in the RPE and photoreceptor cellular organelles may contribute to KCNJ13-related retinal degeneration and provide a therapeutic target.