Significant Visual Impairment Research Articles

Identification of 12 OCA Cases in Chinese Population and Two Novel Variants.

OCA (oculocutaneous albinism) refers to a group of heterogeneous congenital disorders of which the common manifestations are variable degrees of cutaneous hypopigmentation and significant visual impairment, including poor visual acuity, photophobia, and nystagmus. Molecular analysis may elucidate its pathogenesis and be in favor of accurate diagnosis. High-throughput sequencing and Sanger sequencing were performed to detect mutational alleles and in silico analysis was performed for prediction of variant pathogenicity. Ten TYR-related and two OCA2-related patients were identified with 16 different variants with potential pathogenicity. Two novel missense variants [TYR: c.623T > G, p(Leu208Arg) and OCA2: c.1325A > G, p(Asn442Ser)] are identified in this study, and three OCA cases are reported for the first time in Chinese population based on their associated variants. Analysis of crystal structures of TYR ortholog and its paralog TYRP1 suggests that the substitution of Leu208 may have an impact on protein stability. This study may facilitate OCA diagnosis by expanding the mutational spectrum of TYR and OCA2 as well as further basic studies about these two genes.

A Review of Pathologic Myopia.

Pathologic myopia is a leading cause of vision loss worldwide and is most prevalent in developed nations in East and Southeast Asia. Although the pathophysiologic mechanisms behind pathologic myopia have yet to be elucidated, the process is thought to stem from excessive axial elongation of the globe and subsequent degeneration of vital structures within the posterior segment. The array of complications that arise from this condition can lead to significant visual impairment. The purpose of this article is to review the classification, pathophysiology, complications, and management of pathologic myopia.

Current and Novel Therapeutic Approaches for Treatment of Diabetic Macular Edema.

Diabetic macular edema (DME) is a major ocular complication of diabetes mellitus (DM), leading to significant visual impairment. DME’s pathogenesis is multifactorial. Focal edema tends to occur when primary metabolic abnormalities lead to a persistent hyperglycemic state, causing the development of microaneurysms, often with extravascular lipoprotein in a circinate pattern around the focal leakage. On the other hand, diffusion edema is due to a generalized breakdown of the inner blood–retinal barrier, leading to profuse early leakage from the entire capillary bed of the posterior pole with the subsequent extravasation of fluid into the extracellular space. The pathogenesis of DME occurs through the interaction of multiple molecular mediators, including the overexpression of several growth factors, including vascular endothelial growth factor (VEGF), insulin-like growth factor-1, angiopoietin-1, and -2, stromal-derived factor-1, fibroblast growth factor-2, and tumor necrosis factor. Synergistically, these growth factors mediate angiogenesis, protease production, endothelial cell proliferation, and migration. Treatment for DME generally involves primary management of DM, laser photocoagulation, and pharmacotherapeutics targeting mediators, namely, the anti-VEGF pathway. The emergence of anti-VEGF therapies has resulted in significant clinical improvements compared to laser therapy alone. However, multiple factors influencing the visual outcome after anti-VEGF treatment and the presence of anti-VEGF non-responders have necessitated the development of new pharmacotherapies. In this review, we explore the pathophysiology of DME and current management strategies. In addition, we provide a comprehensive analysis of emerging therapeutic approaches to the treatment of DME.

Potential Prognostic Indicators for Patients With Retinal Vein Occlusion.

The second most prevalent cause of retinal vascular disease is retinal vein occlusion (RVO). RVO raises intravascular pressure in the capillary and veins, triggering vessel barrier collapse and subsequent leaking of blood or plasma components into the tissue (edema). Macular edema (ME) is a major complication of RVO that results in significant visual impairment. Laser therapy, intravitreal steroid injections, and vascular endothelial growth factor (VEGF) inhibitors are the major therapeutic techniques. Different therapies reduce ME of RVO and improve visual activity. However, some people have no impact on the resolution of ME, while others have a poor visual prognosis despite full ME cure. There are many investigators who studied the relationship between indicators of various instruments with visual activity. However, a summary of those findings is currently lacking. Therefore, we will focus on the predictive factors of different studies associated with positive visual activity outcomes, which would be very useful and important to help address both treatment expectations and methods for patients with RVO.

Q&A: Rating Horner Syndrome

QUESTION: How is Horner syndrome rated?ANSWER: Horner syndrome is a relatively rare, usually unilateral disorder characterized by a constricted pupil (miosis), drooping of the upper eyelid (ptosis), and absence of facial sweating (anhidrosis). It results from disruption of the sympathetic nerve supply to the face, including the eye. The neural disruption can be caused by many different diseases and injuries, both congenital and acquired, and some cases are idiopathic.The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) does not specifically address Horner syndrome. However, in the sixth edition, ptosis can be rated using Table 11-5, Criteria for Rating Impairment due to Facial Disorders and/or Disfigurement (6th ed, 262), as explained in Section 11.3a, Criteria for Rating Impairment due to Facial Disorders and/or Disfigurement (6th ed, 261-265). Usually, Horner syndrome does not result in significant visual impairment. However, Chapter 12, The Visual System, Section 12.4b, Individual Adjustments (6th ed, 305-306), explains considerations for other functions. In the unlikely event the ptosis is of sufficient severity to restrict the visual field, that impairment can be rated. Because miosis often helps correct visual acuity deficit from astigmatism, there is usually no visual acuity loss from Horner syndrome.

Quality of Life and Its Association with Level of Functioning in Young Children with Cerebral Palsy.

Quality of life (QOL) in older children, adolescents, and adults with cerebral palsy (CP) is significantly impaired. Level of functioning is one of the probable determinants of impairment in QOL. However, such studies in young children with CP are scarce in the literature. Parents of all consecutive children aged between 1 and 4 years with a confirmed diagnosis of CP completed the Infant Toddler Quality of Life (ITQOL) questionnaire. Total and individual subdomain scores of ITQOL were examined for association with the level of functioning measured by Gross Motor Function Classification System-Expanded & Revised (GMFCS E&R), Mini-Manual Ability Classification System (Mini-MACS), Communication Function Classification System (CFCS), and Eating and Drinking Ability Classification System (EDACS), with/without adjustment to probable confounding variables. One hundred three children with CP (74 boys, mean age: 2.6 ± 0.9 years, 49% lower and 39% middle socioeconomic status) were enrolled. All four scales (GMFCS, Mini-MACS, CFCS, and EDACS) describing levels of functioning had significant association with ITQOL total score (β= -0.19, -0.15, -0.11, -0.09, respectively), which persisted even after adjusting for confounding variables (p = 0.004, 0.01, 0.03, and 0.046, respectively). Among the confounding variables, uncontrolled seizures, significant vision impairment, lower socioeconomic status, type of CP, and institution of comprehensive rehabilitation measures for ≥6 months had a significant association with ITQOL score (p = 0.03, 0.04, 0.02, 0.02, and 0.01, respectively). Level of functioning as measured by GMFCS, Mini-MACS, EDACS, and CFCS is independent predictors of impairment in QOL in young children with CP.

Visual functional defects in patients with type 2 diabetes mellitus: a questionnaire based cross-sectional study.

To determine the impact of type 2 diabetes mellitus (T2DM) on visual functions, identify different modifiers as risk or protective factors, and find out how these factors affect patients' visual symptoms and visual functions as a whole. We performed an online survey among 1030 participants (400 patients, 630 non-patients). Demographic features and severity of disease were documented, while visual functions were evaluated using National Eye Institute Visual Functioning questionnaire-25 (NEI VFQ-25). Independent t-test, analysis of variance, linear and nonlinear regression models were used to assess all data. Scores other than color vision among T2DM patients were significantly lower compared with non-T2DM participants. There was significant difference after stratification of age and education, but no significant difference between different genders was observed. Parameters including duration of T2DM, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) negatively impacted on the scores, with 20years' of diabetic duration, 10mmol/L of FPG, 7.5% of HbA1c being potential cut-off points. Poorer best corrected visual acuity (BCVA) and diagnosis of diabetic retinopathy were risk factors, while they simultaneously produced mediation effect, contributing 5%-78% of effect in the deterioration of visual functions caused by longer diabetic duration and higher blood glucose. Significant visual impairments and faster deterioration in visual functions were seen in T2DM patients, with older age, lower educational level, longer diabetic duration, poorer blood glucose administration, limited BCVA, and the presence of diabetic retinopathy identified as risk factors. Average BCVA and diabetic retinopathy also yielded mediation effect as diabetic duration lengthened and blood glucose elevated.

Protective Effects of Spirulina maxima against Blue Light-Induced Retinal Damages in A2E-Laden ARPE-19 Cells and Balb/c Mice.

Age-related macular degeneration (AMD) is a significant visual impairment in older people, and there is no treatment for dry AMD. Spirulina maxima (S. maxima), a cyanobacterium, has inhibitory effects against oxidative stress. However, the protective effects of S. maxima and its underlying mechanisms on blue light (BL)-caused macular degeneration are unknown. We aimed to investigate the protective effects of S. maxima on blue light-caused retinal damage and demonstrate its underlying mechanisms in human retinal pigment epithelial (ARPE-19) cells and Balb/c retinas. Additionally, the active component of S. maxima was examined in the RPE cells. In vitro, S. maxima decreased BL-induced RPE cell death by inhibiting reactive oxygen species (ROS) production. S. maxima inhibited BL-induced inflammation via regulating the NF-κB pathway, inflammatory-related gene expression, and the apoptosis pathway in RPE cells. In vivo, administration of S. maxima inhibited BL-induced retinal degeneration by restoring the thicknesses of whole retina, ONL (outer nuclear layer), INL (inner nuclear layer), and PL (photoreceptor layer) by BL exposure. Phycocyanin exerted protective effects in the pre-and post-treatment system. Therefore, S. maxima could be a potential nutraceutical approach to intercept the patho-physiological processes leading to dry AMD and advancement to wet AMD. Moreover, phycocyanin was a major active compound of S. maxima. These findings need to be investigated in human studies, particularly through a clinical trial.

Некоторые аспекты глазного и глазокожного альбинизма

The article provides an overview of the literature on the aspects of eye and eye albinism, as the epidemiology of hereditary diseases is an important tool for describing the level of genetic health of populations. Albinism refers to diseases of amino acid metabolism, which is based on a hereditary or resulting from mutations defect of metabolism of melanin. The relevance of the research is due to the significant decrease in visual acuity characteristic of this pathology, leading to a violation of the patient's quality of life and disability. The role of melanin in the body is essential, but has not yet been fully studied. Along with other functions, melanin provides normal formation and development of the fetal nervous system. In the case of albinism there is an abnormal crossing of ganglion cells in chiasm, the number of unreconstructed fibers is significantly reduced, which causes a violation of the normal retinotopic organization of the lateral cranked nucleus. The article provides a classification of varieties of albinism, based on data from genetic studies and describes the phenotypic characteristics of these varieties. The syndromes of German–Pudlak and Chediac–Higashi, and a number of other disorders of melanin formation are mentioned. The review of literature has led to the conclusion that in modern ophthalmology and genetics to albinism include at least 10 forms of disease and a large number of syndromes with an associated decrease in pigmentation with characteristic clinical manifestations and types of inheritance. They are always based on a hereditary or mutation-related defect of the metabolism of melanin disease, and the symptom complex includes significant visual impairments that cause visual impairment, reduce the quality of life and require the creation of special conditions for the training and subsequent employment of patients, which makes the research of albinism in ophthalmology constant. Key words: congenital pathology, eye-skin albinism, eye albinism, melanin, tyrosinase.

Ocular inflammatory manifestations following COVID-19 vaccinations in Taiwan: A case series.

As a continuing demand for booster shots against SARS-CoV-2, ocular adverse events following the coronavirus disease-2019 (COVID-19) vaccines can cause significant visual impairment, and they warrant a high awareness and detailed documentation of possible ocular inflammatory manifestations. We present a case series of 11 patients presenting with ocular manifestations relevant to vaccine-associated autoimmune response within 6 weeks after the vaccination of the Oxford-AstraZeneca, the Moderna, and Pfizer-BioNTech vaccines at the main tertiary referral center in the most populated and most vaccinated city in Taiwan. Their diagnosis included five acute anterior uveitis, two multiple evanescent white dot syndrome, one probable Vogt-Koyanagi-Harada disease, one anterior scleritis, one relapsed idiopathic panuveitis, and one autoantibody-related central retinal artery occlusion. This report presented a broad spectrum of the ocular inflammatory events following the vaccination of COVID-19. Early recognition of the clinical manifestations mentioned herein with prompt management is crucial in recovering the patients' vision.

Correcting Presbyopia With Autofocusing Liquid-Lens Eyeglasses.

Presbyopia, an age-related ocular disorder, is characterized by the loss in the accommodative abilities of the human eye. Conventional methods of correcting presbyopia divide the field of view, thereby resulting in significant vision impairment. We demonstrate the design, assembly and evaluation of autofocusing eyeglasses for restoration of accommodation without dividing the field of view. The adaptive optics eyeglasses comprise of two variable-focus liquid lenses, a time-of-flight range sensor and low-power, dual microprocessor control electronics, housed within an ergonomic frame. Subject-specific accommodation deficiency models were utilized to demonstrate high-fidelity accommodative correction. The abilities of this system to reduce accommodation deficiency, its power consumption, response time, optical performance and MTF were evaluated. Average corrected accommodation deficiencies for 5 subjects ranged from -0.021 D to 0.016 D. Each accommodation correction calculation was performed in ∼67 ms which consumed 4.86 mJ of energy. The optical resolution of the system was 10.5 cycles/degree, and featured a restorative accommodative range of 4.3 D. This system was capable of running for up to 19 hours between charge cycles and weighed ∼132 g. The design, assembly and performance of an autofocusing eyeglasses system to restore accommodation in presbyopes has been demonstrated. The new autofocusing eyeglasses system presented in this article has the potential to restore pre-presbyopic levels of accommodation in subjects diagnosed with presbyopia.

Computer vision syndrome: Symptoms, risk factors, and practices.

According to computer vision syndrome (CVS). Due to constant use of computers by the students, it has become one of the growing health risks associated with technology (cell phones and tablets). CVS is a combination of eye and vision disorders associated with activities that affect near vision and is experienced in relation to or during the use of computers. The main aim of the study was to find the risk factors of CVS, its symptoms, and other factors associated with CVS. In this cross-sectional study, data was collected using a purposely constructed E-questionnaire. The questionnaire consisted of demographic items and items related to the usage of E-devices and the symptoms of eye problems. After data collection, data was coded and entered in the Statistical Package for the Social Sciences (SPSS) ver. 20 software for analyses. Descriptive statistics (mean and standard deviation, frequencies and percentages) were computed. To measure the significant differences, Chi-square test was used at 5% level of significance. The mean (SD) age of 400 respondents was 22.5 (11.5) years. We computed the internal consistency, and the overall Cronbach alpha was 0.81. Also, 40% of the respondents were females, while 60% were males. Results showed that 20% of the respondents had multiple symptoms of eye problems, while 9% had no symptoms, 9% had eye pain, 8% had dryness of eye, and 6% had watering of eyes and redness of eye symptoms. The rest of the symptoms was found in less than 5% of the respondents. This worldwide issue requires immediate attention. Long-term computer use has been linked to significant visual impairments, particularly in people who use computers and similar gadgets for extended periods of time.

Clinical profile of amblyopia and outcome of occlusion therapy in pediatric populations attending a referral hospital

AIM: To study clinical profile of amblyopia and also the outcomes of occlusion therapy among the amblyopes. METHODS: This was a hospital-based longitudinal study by design. Data were collected from April 2015 to April 2016 in Ophthalmology Department of Dhulikhel Hospital. Presenting visual acuity, chief complaint at presentation, age at presentation, refractive status, binocularity and fixation patterns were assessed in all the children with amblyopia. Improvement in visual acuity was also noted in all the subjects after occlusion therapy, which is a most commonly used modality of treatment for amblyopia. RESULTS: Among 1092 children examined during the study period, 60 (5.49%) were amblyopic. Among them, 35 (58.30%) were females and 25 (41.70%) were males. The mean age at presentation was 8.87±3.29y. Meridional amblyopia was the most prevalent subtype seen in 43.3% (n=26) of children followed by anisohypermetropic amblyopia (20%, n=12). The most common refractive error was astigmatism accounting for 58.30% of the total cases followed by hypermetropia (22.5%) and myopia (7.5%). Compliance with spectacle wear combined with occlusion therapy and active vision therapy was 73.3% (n=44). There was a statistically significant improvement in visual acuity of the amblyopic eyes after the different treatment strategies after 3mo (P=0.002). CONCLUSION: Prevalence of amblyopia and associated visual impairment is still a public health issue in developing countries like Nepal. Lack of awareness and lack of community or preschool vision screening for children lead to late presentation and significant visual impairment associated with the condition. The burden can easily be reduced with screening camps, timely referrals and proper interventions.

Visual acuity and anatomical changes following vitrectomy for epiretinal membrane foveoschisis: a case series

PurposeTo evaluate the visual outcome and macular anatomic structures on spectral-domain optical coherence tomography (SD-OCT) of patients with epiretinal membrane (ERM) foveoschisis who underwent vitrectomy.MethodsA retrospective cohort, interventional, case series.ParticipantsFourteen patients (14 eyes) with central vision loss from an ERM foveoschisis underwent vitrectomy at Chiang Mai University Hospital from 2017 to 2018 and had a follow-up period of 12 months.InterventionsThe 23G vitrectomy with ERM and internal limiting membrane (ILM) peeling was performed by a single surgeon.Main outcomesBest-corrected visual acuity (BCVA) and anatomic appearance on SD-OCT were assessed at the time of preoperative evaluations and post-operative follow-ups at 1, 3, 6, and 12 months.ResultsFourteen patients with a mean (SD) age of 67.9 (7.9) years and a mean (SD) visual acuity (VA) of 0.6 (0.1) LogMAR units were included in this study. Significant VA improvements were observed at the 3-month (0.43 (0.14) LogMAR unit), 6-month (0.45 (0.16) LogMAR unit) and 12-month (0.37 (0.21) LogMAR unit) post-operative visits compared to baseline, all with P-values < 0.001. At month 12, there were vision improvements of ≥3 lines in 8 (57.2%) patients, vision improvements of 1 or 2 lines in 2 (14.3%) patients, vision remained at the same line of pre-operation in 3 (21.4%) patients, and vision decreased by 1 line in 1 (7.1%) patient. Regarding the anatomical outcomes, 13 (92.9%) patients achieved anatomical foveal restoration, while one had persistent intraretinal schisis at the 12-month follow-up. The median time to achieve a foveal restoration was 3 months. No significant visual impairments were observed post-operatively.ConclusionIn patients with central vision loss from ERM foveoschisis, vitrectomy with ILM stripping tended to improve both visual and anatomical outcomes.

A Patient With Optic Nerve Pit Maculopathy Successfully Treated With Juxtapapillary Laser Photocoagulation

Optic disc pits are rare and congenital or acquired anomalies of the optic disc, usually remaining asymptomatic. However, serous macular detachment or optic disc maculopathy is the most common complication, causing significant visual deterioration, without a current consensus about treatment. A 55-year-old woman with a past medical history of diabetes mellitus and systemic hypertension was referred for an abnormal finding in the retina. The Corrected Distance Visual Acuity (CDVA) was 20/40 in the right eye and 20/30 in the left eye. Marcus-Gunn was negative and Slit-lamp biomicroscopy revealed no pathologic findings in both eyes. Funduscopic examination showed an excavation in the inferotemporal part of the Optic Nerve Head (ONH) with serous macular detachment extending to the optic disc. Based on clinical examination and paraclinical imaging fluorescein Angiogeraphy (FAG) Optical Coherence Tomography (OCT), optic pit maculopathy was diagnosed and the patient underwent Juxtapapillary Laser Photocoagulation (JLP). After 2 years of follow-up, there were anatomical and functional improvements.

STAT3-Specific Single Domain Nanobody Inhibits Expansion of Pathogenic Th17 Responses and Suppresses Uveitis in Mice.

STAT3 activates transcription of genes that regulate cell growth, differentiation, and survival of mammalian cells. Genetic deletion of Stat3 in T cells has been shown to abrogate Th17 differentiation, suggesting that STAT3 is a potential therapeutic target for Th17-mediated diseases. However, a major impediment to therapeutic targeting of intracellular proteins such as STAT3 is the lack of efficient methods for delivering STAT3 inhibitors into cells. In this study, we developed a novel antibody (SBT-100) comprised of the variable (V) region of a STAT3-specific heavy chain molecule and demonstrate that this 15 kDa STAT3-specific nanobody enters human and mouse cells, and induced suppression of STAT3 activation and lymphocyte proliferation in a concentration-dependent manner. To investigate whether SBT-100 would be effective in suppressing inflammation in vivo, we induced experimental autoimmune uveitis (EAU) in C57BL/6J mice by active immunization with peptide from the ocular autoantigen, interphotoreceptor retinoid binding protein (IRBP651-670). Analysis of the retina by fundoscopy, histological examination, or optical coherence tomography showed that treatment of the mice with SBT-100 suppressed uveitis by inhibiting expansion of pathogenic Th17 cells that mediate EAU. Electroretinographic (ERG) recordings of dark and light adapted a- and b-waves showed that SBT-100 treatment rescued mice from developing significant visual impairment observed in untreated EAU mice. Adoptive transfer of activated IRBP-specific T cells from untreated EAU mice induced EAU, while EAU was significantly attenuated in mice that received IRBP-specific T cells from SBT-100 treated mice. Taken together, these results demonstrate efficacy of SBT-100 in mice and suggests its therapeutic potential for human autoimmune diseases.

Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection

Viral infections of the cornea including herpes simplex virus 1 (HSV-1) cause visual morbidity, and the corneal endothelial cell damage leads to significant visual impairment. Interferon regulatory factor 7 (IRF7) has been identified as a significant regulator in corneal endothelial cells after an HSV-1 infection. To examine the role played by IRF7, the DNA binding domain (DBD) of IRF7 of human corneal endothelial cells (HCEn) was disrupted. An RNAi inhibition of IRF7 and IRF7 DBD disruption (IRF7 ∆DBD) led to an impairment of IFN-β production. Impaired IFN-β production by IRF7 ∆DBD was regained by IRF7 DNA transfection. Transcriptional network analysis indicated that IRF7 plays a role in antigen presentation function of corneal endothelial cells. When the antigen presentation activity of HCEn cells were examined for priming of memory CD8 T cells, IRF7 disruption abolished the anti-viral cytotoxic T lymphocyte (CTL) response which was dependent on the major histocompatibility complex (MHC) class I. To further examine the roles played by IRF7 in CTL induction as acquired immunity, the contribution of IRF7 to MHC class I-mediated antigen presentation was assessed. Analysis of IRF7 ∆DBD cells indicated that IRF7 played an unrecognized role in MHC class I induction, and the viral infection induced-MHC class I induction was abolished by IRF7 disruption. Collectively, the IRF7 in corneal endothelial cells not only contributed to type I IFN response, but also to the mediation of viral infection-induced MHC class I upregulation and priming of CD8 arm of acquired immunity.

Follow-up rates for patients needing regular intravitreal therapy in rural north-western Western Australia.

Regular intravitreal injections are an important treatment for significant vision impairment caused by diabetic macular oedema. Barriers to intravitreal treatment for rural Australian patients include travel time to appointments, especially as patients face a high volume of other medical appointments for their diabetes and related co-morbidities. This audit addresses intravitreal injection compliance by identifying patients lost to follow up in north-western Western Australia. A retrospective audit of all injections was performed in the Pilbara and Kimberley between January and December 2018. Outcome measures included total injections, number of injection patients, rates of patients lost to follow-up by region, Aboriginal and Torres Strait Islander status and diagnosis. The audit was extended to include the first 6 months of 2019 to ensure further treatment plan timeframes had lapsed. A total of 140 patients received injections, resulting in 346 injections. Ten patients were excluded due to relocation to another region and three patients were deceased. Seventeen patients were lost to follow-up (12.1%). Of those lost to follow-up, 14.3% were in the Pilbara region and 10% in the Kimberley region. Similar rates with respect to Indigenous status with 12.6% identifying as Aboriginal and 11.4% not. 15.8% were treated for diabetic macular oedema and 3.8% for age-related macular degeneration. The logistics of providing appropriate intravitreal therapy, including scheduling timely visits and working in hospital and community-controlled settings, requires a specific focus on those needing intravitreal treatment. The study highlights the importance of coordination and systems to enable patients to receive injections in remote settings. Further analysis of optimal patient management plans for appropriate frequency and treatment outcomes is required.

Gene therapy for inherited retinal diseases.

Inherited retinal diseases (IRDs) are a genetically variable collection of devastating disorders that lead to significant visual impairment. Advances in genetic characterization over the past two decades have allowed identification of over 260 causative mutations associated with inherited retinal disorders. Thought to be incurable, gene supplementation therapy offers great promise in treating various forms of these blinding conditions. In gene replacement therapy, a disease-causing gene is replaced with a functional copy of the gene. These therapies are designed to slow disease progression and hopefully restore visual function. Gene therapies are typically delivered to target retinal cells by subretinal (SR) or intravitreal (IVT) injection. The historic Food and Drug Administration (FDA) approval of voretigene neparvovec for RPE65-associated Leber’s congenital amaurosis (LCA) spurred tremendous optimism surrounding retinal gene therapy for various other monogenic IRDs. Novel disease-causing mutations continue to be discovered annually, and targeted genetic therapy is now under development in clinical and preclinical models for many IRDs. Numerous clinical trials for other IRDs are ongoing or have recently completed. Disorders being targeted for genetic therapy include retinitis pigmentosa (RP), choroideremia (CHM), achromatopsia (ACHM), Leber’s hereditary optic neuropathy, usher syndrome (USH), X-linked retinoschisis, and Stargardt disease. Here, we provide an update of completed, ongoing, and planned clinical trials using gene supplementation strategies for retinal degenerative disorders.

Vernal keratoconjunctivitis and keratoconus.

Vernal keratoconjunctivitis (VKC) is a severe allergic inflammatory disease affecting the conjunctiva in children and young adults. Keratoconus (KC) is a progressive corneal disease characterized by thinning of the corneal stroma, increased and asymmetric corneal curvature, with a potential for significant visual deterioration and is one of the most common corneal complications of VKC. We aimed to review the association of these two diseases, with focus on the mechanisms, prevalence, natural history and treatment strategies of KC associated with VKC. KC is a common complication of VKC. KC prevalence can be as high as 26.8% among VKC patients, whereas abnormal corneal topography may appear in up to 71% of them. It is more severe and progresses faster in the setting of VKC (P < 0.05), with remarkable visual deterioration and with an increased need for keratoplasty. Crosslinking treatment and corneal transplantation appear to be as effective for KC patients with VKC as compared to the patients without VKC. However, postoperative complications are higher in patients with VKC and demand close monitoring, tight control of local inflammation and prompt awareness with consequent restrain of eye rubbing. Patients with VKC should be closely monitored for KC. Prompt recognition of VKC and KC allows tight control of KC pathogenesis mechanisms, timely management of KC progression and preservation of vision and quality of life of young patients.