Advances in gene therapy and genome editing give hope that new treatments will soon be available for inherited eye diseases that together affect a significant proportion of the adult population. New solutions are needed to make genetic diagnosis fast and affordable. This is the first study of such a large group of patients with inherited retinal dystrophies (IRD) and inherited optic neuropathies (ION) in the Polish population. It is based on four years of diagnostic analysis using a broad, targeted NGS approach. The results include the most common pathogenic variants, as well as 91 novel causative variants, including frameshifts in the cumbersome RPGR ORF15 region. The high frequency of the ABCA4 complex haplotype p.(Leu541Pro;Ala1038Val) was confirmed. Additionally, a deletion of exons 22-24 in USH2A, probably specific to the Polish population, was uncovered as the most frequent copy number variation. The diagnostic yield of the broad NGS panel reached 64.3% and is comparable to the results reported for genetic studies of IRD and ION performed for other populations with more extensive WES or WGS methods. A combined approach to identify genetic causes of all known diseases manifesting in the posterior eye segment appears to be the optimal choice given the currently available treatment options and advanced clinical trials.

Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare disease characterized by accumulation of yellowish deposits in the macula. Rarely, it may be complicated by choroidal neovascularization (CNV). Cases with CNV may be confused with occult CNV in age-related macular degeneration. In our case, we will present the visual and anatomical results of a patient with AOVF-related CNV, in which we administered 3 doses of intravitreal ranibizumab (IVR). A 59-year-old female patient, who attended our clinic with the complaint of decreased vision in both eyes, was diagnosed with AOVF-related CNV in both eyes and was treated with 3 doses of IVR for 3 months. Despite the improvement in visual and anatomical functions 1 month after the first dose, vision decreased, and anatomical functions regressed to the pre-injection state in continued injections. IVR therapy is not an appropriate treatment option in the treatment of AOVF-associated CNV.

UNASSIGNED: Acyl-CoA binding domain containing 5 (ACBD5) deficiency is a newly defined inborn peroxisomal disorder with only 7 patients reported to date. Herein, we report a patient with ACBD5 deficiency who was diagnosed after a complicated diagnostic process.
UNASSIGNED: A 6-year-old male patient was admitted with complaints of neuromotor regression and visual disturbances. He had spastic paraparesis dominated with axial hypotonic posturing and horizontal nystagmus. His very-long-chain fatty acid levels were within normal ranges with a slightly elevated C26:0/C22:0 ratio. Brain magnetic resonance imaging revealed white matter involvement. Clinical exome sequencing displayed a novel homozygous intronic splice site variant (c.936 + 2T>G) in the ACBD5 (NM_145698.5) gene.
UNASSIGNED: With this report, a novel variant in ACBD5 deficiency was described. Macular dystrophy was demonstrated with optical coherence tomography imaging for the first time in the literature in ACBD5 deficiency. In order to contribute to the knowledge about the clinical, biochemical, and genetic spectrum of ACBD5 deficiency, new patients need to be defined.

Eye-related diseases, specifically retinal dystrophy (RD) conditions, are the leading cause of blindness worldwide. Gene addition, regulation, or editing could potentially treat such diseases through gene expression regulation. CRISPR/Cas9 gene editing is one of the most prominent and precise gene editing tools which could be employed to edit genes related to the dystrophic condition. However, CRISPR/Cas9 faces in vivo delivery challenges due to its high molecular weight, negative charge, prone to degradation in the presence of nucleases and proteases, poor cellular degradation, etc., which makes it challenging to adopt for therapeutic applications. We developed cRGD-modified lipopolymeric nanoplexes loaded with Cas9 RNPs with a particle size and zeta potential of 175 ± 20 nm and 2.15 ± 0.9 mV, respectively. The cRGD-modified lipopolymeric nanoplexes were stable for 194 h and able to transfect >70 % ARPE-19 and NIH3T3 cells with an Indel frequency of ~40 % for the VEGF-A gene. The cRGD-modified lipopolymeric nanoplexes found good vitreous mobility and could transfection retinal cells in vivo after 48 h of intravitreal injection in Wistar Rats. Moreover, in vivo VEGFA gene editing was ~10 % with minimal toxicities. Collectively, the cRGD-modified lipopolymeric nanoplexes were found to have extreme potential in delivering CRISPR/Cas9 RNPs payload to the retinal tissues for therapeutic applications.

Purpose: Advancements in retinal imaging have augmented our understanding of the pathology and structure-function relationships of retinal disease. No single diagnostic test is sufficient; rather, diagnostic and management strategies increasingly involve the synthesis of multiple imaging modalities. Methods: This literature review and editorial offer practical clinical guidelines for how the retina specialist can use multimodal imaging to manage retinal conditions. Results: Various imaging modalities offer information on different aspects of retinal structure and function. For example, optical coherence tomography (OCT) and B-scan ultrasonography can provide insights into the microstructural anatomy; fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT angiography (OCTA) can reveal vascular integrity and perfusion status; and near-infrared reflectance and fundus autofluorescence (FAF) can characterize molecular components within tissues. Managing retinal vascular diseases often includes fundus photography, OCT, OCTA, and FA to evaluate for macular edema, retinal ischemia, and the secondary complications of neovascularization (NV). OCT and FAF play a key role in diagnosing and treating maculopathies. FA, OCTA, and ICGA can help identify macular NV, posterior uveitis, and choroidal venous insufficiency, which guides treatment strategies. Finally, OCT and B-scan ultrasonography can help with preoperative planning and prognostication in vitreoretinal surgical conditions. Conclusions: Today, the retina specialist has access to numerous retinal imaging modalities that can augment the clinical examination to help diagnose and manage retinal conditions. Understanding the capabilities and limitations of each modality is critical to maximizing its clinical utility.

Alstrom\'s syndrome (AS) is an autosomal recessively inherited multisystemic disorder that falls under the umbrella of ciliopathy. It is characterized by poor vision, hearing impairment, cardiomyopathy, childhood obesity, diabetes mellitus type 2, dyslipidemia, pulmonary, hepatic, and renal failure besides systemic fibrosis. Biallelic pathogenic variants in ALMS1 gene cause AS. Retrospective study (1990-2017) included 12 Saudi patients with AS based on their phenotype, biochemical markers, and genotype. The study was approved by Fisal Specialist Hospital and Research Centre, Riyadh (RAC number 2131129) on October 2, 2012. This study showed clinical and genetic heterogeneity; six patients showed a founder mutation (IVS18-2A > T in exon 19), whereas six others showed private mutations. AS in Saudi Arabia is underdiagnosed probably because of its variable clinical manifestations. We report 12 Saudi patients with AS to enhance the awareness about this syndrome.

Advancements in ocular imaging have significantly broadened our comprehension of mitochondrial retinopathies and optic neuropathies by examining the structural and pathological aspects of the retina and optic nerve in these conditions. This article aims to review the prominent imaging characteristics associated with mitochondrial retinopathies and optic neuropathies, aiming to deepen our insight into their pathogenesis and clinical features. Preceding this exploration, the article provides a detailed overview of the crucial genetic and clinical features, which is essential for the proper interpretation of in vivo imaging. More importantly, we will provide a critical analysis on how these imaging modalities could serve as biomarkers for characterization and monitoring, as well as in guiding treatment decisions. However, these imaging methods have limitations, which will be discussed along with potential strategies to mitigate them. Lastly, the article will emphasize the potential advantages and future integration of imaging techniques in evaluating patients with mitochondrial eye disorders, considering the prospects of emerging gene therapies.

BACKGROUND: The aim of the study was to detect the changes in retinal and choroidal vasculature via optical coherence tomography angiography (OCTA) by comparing the quantitative OCTA parameters in patients with and without myotonic dystrophies (DM).
METHODS: The cross-sectional study. Forty-one consecutive patients affected by DMs were enrolled. The inclusion criteria were molecular diagnosis of DM types 1 and 2. To avoid the age effect on microvascular changes and to justify a comparison between DM1 and DM2 patients, two control groups matched for sex and age were established.
RESULTS: The vascular density was found to be significantly decreased in the DM groups compared to the controls in the macular, parafoveal and perifoveal zone of superficial capillary plexus (p < 0.001 for the DM1 group, and p = 0.001, p = 0.005 and p = 0.026, respectively, for the DM2 group), as well as in the macular zone in the deep capillary plexus for DM1 (p = 0.002) and deep macular and perifoveal zone for DM2 (p = 0.007, p = 0.001, respectively). The foveal avascular zone showed no significant differences between DM1 and DM2 compared to their control groups (p = 0.320 and p = 0.945, respectively).
CONCLUSIONS: Our results show that DM is associated not only with the classic pigmentary changes but also with superficial and deep retinal microvasculature abnormalities, suggesting that these changes may be related to local hypoperfusion. Optical coherence tomography angiography is a useful tool for the diagnosis and characterization of retinal changes in DM and should be part of the standard evaluation of these patients.

BACKGROUND: To determine the effectiveness of bone marrow-derived mesenchymal stem cell therapy on visual acuity and visual field in patients with retinitis pigmentosa.
OBJECTIVE: Stem cell treatment in retinitis pigmentosa provides improvement in visual acuity and visual field.
METHODS: Forty-seven eyes of 27 patients diagnosed with retinitis pigmentosa were included in our study. Allogeneic bone marrow-derived mesenchymal stem cells were administered by deep subtenon injection. Complete routine ophthalmological examinations, optical coherence tomography (Zeiss, Cirrus HD-OCT) measurements, and visual field (Humphrey perimetry, 30-2) tests were performed on all patients before the treatment and on the 1st, 3rd, and 6th month after treatment. The best corrected visual acuities of the patients were determined by the Snellen chart and converted to logMAR. Visual evoked potential (VEP) and electroretinogram (ERG) examinations of the patients before the treatment and on the 6th month after the treatment were performed (Metrovision) data were compared.
RESULTS: Visual acuities were 0.74 ± 0.49 logMAR before treatment and 0.61 ± 0.46 logMAR after treatment. Visual acuity had a statistically significant increase (p < 0.001). The visual field deviation was found to be -27.16 ± 5.77 dB before treatment and -26.59 ± 5.96 dB after treatment (p = 0.005). The ganglion cell layer was 46.26 ± 12.87 μm before treatment and 52.47 ± 12.26 μm after treatment (p = 0.003). There was a significant improvement in Pattern VEP 120º P100 amplitude compared to that before the treatment (4.43 ± 2.42 μV) and that after the treatment (5.09 ± 2.86 μV) (p = 0.013). ERG latency measurements were 18.33 ± 15.39 μV before treatment and 20.87 ± 18.64 μV after treatment for scotopic 0.01 (p = 0.02). ERG latency measurements for scotopic 3.0 were 20.75 ± 26.31 μV before treatment and 23.10 ± 28.60 μV after treatment (p = 0.014).
CONCLUSIONS: Retinitis pigmentosa is a progressive, inherited disease that can result in severe vision loss. In retinitis pigmentosa, the application of bone marrow-derived mesenchymal stem cells by deep subtenon injection has positive effects on visual function. No systemic or ophthalmic side effects were detected in the patients during the 6-month follow-up period.

BACKGROUND: To describe different clinical presentations of a same NR2E3 recessive mutation in two families and within one family.
METHODS: Interventional family study.
RESULTS: Our first case was a one-year-old male child with high hyperopia and refractive accommodative esotropia. In retinal examination, peri-papillary sub-retinal fibrosis with a helicoid configuration was observed in both eyes. The parents and the only sibling had no pathologic findings in the eyes. The child showed to have severely reduced responses in both photopic and scotopic electroretinogram components. In the genetic investigation, a homozygous autosomal recessive mutation in the NR2E3 gene (IVS1-2A > C) was discovered in the affected child, while the other family members were heterozygous for this mutation. We followed up with the patient for 3 years and no new lesion developed during this period. The second case was a 13-year-old male child referred to the retina clinic for decreased vision in the right eye. In retina examination, there were nummular pigmentary changes at the level of retinal pigment epithelium and along the vascular arcades with foveo-schitic changes in both eyes. A choroidal neovascularization (CNV) was noticed in the macula of his right eye. The genetic evaluation proved the same mutation in the NR2E3 gene as in the first case. Family history was remarkable for an uncle, an aunt, and two cousins with night blindness.
CONCLUSIONS: Same NR2E3 gene mutation can cause heterogeneous clinical manifestations such as slight retinal changes in the absence of any visual symptoms to high hyperopia associated with helicoid peri-papillary sub-retinal fibrosis.