Long-term follow-up demonstrates change in conformation shape of the focal choroidal excavation lesions.

PURPOSE: This study aims to present long-term observation of 5 eyes with focal choroidal excavation (FCE), focusing on morphological changes in conformity of the lesion. METHODS: A retrospective case series was conducted, including 5 eyes of 5 patients with FCE. The study utilized multimodal imaging including color fundus photography, optical coherence tomography (OCT), enhanced depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), red free imaging, and OCT angiography. RESULTS: The mean age at diagnosis was 51 ± 10.65 years, with a mean follow-up period 37 ± 13.59 months. All cases were unilateral, with 1 presenting FCE as an isolated lesion, and one patient exhibiting 2 FCEs in one eye. The mean choroidal thickness measured by EDI-OCT was 268.2 ± 63.39 µm in the affected eye. One patient displayed choroidal thickening and pachyvessels. Of the 5 eyes, one had conforming and 4 non-conforming FCE. We observed a conversion in conformity in all patients, with 4 cases transitioning from non-conforming FCE to conforming type (3 spontaneously, 1 treatment-induced). In conforming FCE, a hyporeflective space appeared twice between neuroretina and retinal pigment epithelium with spontaneous regression. CONCLUSION: We observed change in shape from the conforming to non-conforming FCE and vice versa in all patients. We consider this small change in the hyporeflective space as non-pathologic and clinically insignificant.

Feasibility of Direct Vitrectomy-Sparing Subretinal Injection for Gene Delivery in Large Animals.

PURPOSE: To assess the safety and feasibility of direct vitrectomy-sparing subretinal injection for gene delivery in a large animal model. METHODS: The experimental Libechov minipigs were used for subretinal delivery of a plasmid DNA vector (pS/MAR-CMV-copGFP) with cytomegalovirus (CMV) promoter, green fluorescent protein (GFP) reporter (copGFP) and a scaffold/matrix attachment region (S/MAR) sequence. The eyes were randomized to subretinal injection of the vector following pars plana vitrectomy (control group) or a direct injection without prior vitrectomy surgery (experimental group). Intra- and post-operative observations up to 30 days after surgery were compared. RESULTS: Six eyes of three mini-pigs underwent surgery for delivery into the subretinal space. Two eyes in the control group were operated with a classical approach (lens-sparing vitrectomy and posterior hyaloid detachment). The other four eyes in the experimental group were injected directly with a subretinal cannula without vitrectomy surgery. No adverse events, such as endophthalmitis, retinal detachment and intraocular pressure elevation were observed post-operatively. The eyes in the experimental group had both shorter surgical time and recovery while achieving the same surgical goal. CONCLUSIONS: This pilot study demonstrates that successful subretinal delivery of gene therapy vectors is achievable using a direct injection without prior vitrectomy surgery.

Subthreshold laser treatment in retinal diseases: a mini review.

PURPOSE: To summarize the mechanism and the clinical applications of subthreshold laser (STL) in retinal practice. Subthreshold or "non-destructive" laser includes all types of laser treatments that produce minimal or no damage to the tissues and no visible signs after application. METHODS: A descriptive review of articles from literature databases (PubMed, Medline, Embase, Cochrane, Web of Science) published before August 2023, which discuss current STL treatments of retinal diseases. RESULTS: This review provides evidence for STL as a treatment option for central serous chorioretinopathy, diabetic retinopathy, age-related macular degeneration, macular edema due to retinal vein occlusion, and other maculopathies. In most published reports, STL has shown a therapeutic effect without damage to the underlying tissue. CONCLUSION: Subthreshold laser treatment has shown safety and efficacy in the management of some retinal and macular diseases. Stimulation of the retinal pigment epithelium without destroying adjacent neuroretina has been shown to be sufficient in inducing retinal repair in many clinical cases. Recent research and clinical studies continue to explore the mechanisms and improving therapeutic benefits of this technology as well as extend the range of retinal disorders treatable by this modality.

Clinical and ocular abnormalities in DEGCAGS syndrome-Developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities.

PURPOSE: To describe clinical and ocular abnormalities in a case of Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome). METHODS: A clinical report. CASE DESCRIPTION: An infant born to a consanguineous Middle Eastern family who was delivered by cesarean section because of in utero growth restriction, premature labor, and breech presentation. Post-partum medical problems included hypotension, generalized hypotonia, bradycardia, apnea requiring resuscitation and positive pressure ventilation, facial dysmorphia, skeletal malformations, and disorders of the gastrointestinal, immune, urinary, respiratory, cardiac, and visual systems. The family reported that a previous child had severe hypotonia at birth and was given the diagnosis of hypoxic ischemic encephalopathy; that child remains on a ventilator in a chronic care facility. Our patient was found to be homozygous for a novel pathogenic missense variant in theZNF699 zinc finger gene on chromosome 19p13 causing a syndrome known as Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome). We review this variable syndrome, including abnormalities of the visual system not described previously. CONCLUSIONS: We describe the 15th child to be presumably identified with the DEGCAGS syndrome and the first individual with homozygous missense variants in the ZNF699 gene who had complete clinical examination and detailed retinal imaging.

Recovery course of persistent posterior subretinal fluid after successful repair of rhegmatogenous retinal detachment.

PURPOSE: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD). METHODS: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented. RESULTS: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks (p < 0.001) and with increased myopia (p = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44-7.47]; p = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21-1.05]; p = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29-1.52]; p = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08-0.88]; p = 0.056). SRF resolution time correlated marginally with prone position. CONCLUSIONS: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year.

Macular hole Delphi consensus statement (MHOST).

PURPOSE: To derive a Delphi method-based consensus for the surgical management of Full Thickness Macular Hole (FTMH) and Lamellar Macular Hole (LMH). METHODS: 37 expert VR surgeons from 21 mainly European countries participated in Delphi method-based questionnaire for diagnosis and treatment of FTMHs and LMHs. RESULTS: A total of 36 items were rated in round 1 by 37 participants, of which 10 items achieved consensus: intraoperative verification of PVD; clinical superiority of OCT-based FTMH classification; practical ineffectiveness of ocriplasmin; circular 360° ILM peeling for small macular holes; use of regular surgical technique for the size of the hole in concomitant retinal detachment; performing complete vitrectomy; SF6 gas as preferred tamponade; cataract surgery if crystalline lens is mildly/moderately opaque; removal of both ILM and LHEP in LMH surgery. In round 2, 18 items with moderate consensus (45-70% agreement) in round 1 were rated by 35 participants. Final consensus was reached in 35% of questions related to both diagnosis and surgical procedures. CONCLUSIONS: This Delphi study provides valuable information about the consensus/disagreement on different scenarios encountered during FTMH and LMH management as a guide tosurgical decision-making. High rate of disagreement and/or variable approaches still exist for treating such relatively common conditions.

Multispectral imaging: Review of current applications.

Multispectral imaging (MSI) is a unique layer-by-layer imaging technique that allows the visualization of a wide array of retinal and choroidal pathologies including retinovascular disorders, retinal pigment epithelial changes, and choroidal lesions. Herein, we summarize the basic imaging principles and current applications of MSI together with recent technology advances in the field. MSI detects reflectance signal from both normal chorioretinal tissue and pathological lesions. Either hyperreflectance or hyporeflectance reveals the absorption activity of pigments such as hemoglobin and melanin and the reflection from interfaces such as the posterior hyaloid. Advances in MSI technique include creation of a retinal and choroidal oxy-deoxy map that could provide a better understanding of blood oxygen saturation within lesions as well as better interpretation of reflectance phenomenon of MSI images such as the different reflectance from the Sattler and Haller layers described in this review.

The impact of artificial intelligence on retinal disease management: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The aim of this review is to define the "state-of-the-art" in artificial intelligence (AI)-enabled devices that support the management of retinal conditions and to provide Vision Academy recommendations on the topic. RECENT FINDINGS: Most of the AI models described in the literature have not been approved for disease management purposes by regulatory authorities. These new technologies are promising as they may be able to provide personalized treatments as well as a personalized risk score for various retinal diseases. However, several issues still need to be addressed, such as the lack of a common regulatory pathway and a lack of clarity regarding the applicability of AI-enabled medical devices in different populations. SUMMARY: It is likely that current clinical practice will need to change following the application of AI-enabled medical devices. These devices are likely to have an impact on the management of retinal disease. However, a consensus needs to be reached to ensure they are safe and effective for the overall population.

Current status and practical considerations of artificial intelligence use in screening and diagnosing retinal diseases: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology. RECENT FINDINGS: In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models. SUMMARY: The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions.

Fundus fluorescein angiography via percutaneous endoscopic gastrostomy: Description of technique.

Purpose: To report an alternative technique of fundus fluorescein angiography using percutaneous endoscopic gastrostomy (PEG). Methods: A case series from a single center. Results: Two bed-bound children on tracheostomy received 10% fluorescein sodium via PEG to diagnose their retinal condition. The dye appeared at 5 min after administration and stayed in the retinal circulation past 30 min. Good quality fluorescein angiograms were obtained in all cases. There were no safety issues in these two children. Conclusions and Importance: Retinal angiography with fluorescein dye administered via percutaneous endoscopic gastrostomy may represent a suitable alternative to currently used intravenous and oral fluorescein angiography.

Visual acuity time in range: a novel concept to describe consistency in treatment response in diabetic macular oedema.

OBJECTIVE: To assess 'time in range' as a novel measure of treatment response in diabetic macular oedema (DMO). METHODS: This post hoc analysis of the Protocol T randomised clinical trial included 660 individuals with centre-involved DMO and best-corrected visual acuity (BCVA) letter score ≤78-≥24 (approximate Snellen equivalent 20/32-20/320). Study participants received intravitreal aflibercept 2.0 mg, repackaged (compounded) bevacizumab 1.25 mg, or ranibizumab 0.3 mg given up to every 4 weeks using defined retreatment criteria. Mean time in range was calculated using a BCVA letter score threshold of ≥69 (20/40 or better; minimum driving requirement in many regions), with sensitivity analyses using BCVA thresholds from 100 to 0 (20/10 to 20/800) in 1-letter increments. RESULTS: Time in range was defined as either the absolute or relative duration above a predefined BCVA threshold, measured in weeks or as a percentage of time, respectively. Using a BCVA letter score threshold of ≥69 (20/40 or better), the least squares mean time in range (adjusted for baseline BCVA) in Year 1 was 41.2 weeks with intravitreal aflibercept, 4.0 weeks longer (95% CI: 1.7, 6.3; p = 0.002) than bevacizumab and 3.6 weeks longer (1.3, 5.9; p = 0.004) than ranibizumab. Overall, mean time in range was numerically longer for intravitreal aflibercept for all BCVA letter score thresholds between 92 and 30 (20/20 to 20/250). In the Day 365-728 analysis, time in range was 3.9 (1.3, 6.5) and 2.4 (0.0, 4.9) weeks longer with intravitreal aflibercept vs bevacizumab and vs ranibizumab (p = 0.011 and 0.106), respectively. CONCLUSION: BCVA time in range may represent another way to describe visual outcomes and potential impact on vision-related functions over time for patients with DMO and provide a better understanding, for physicians and patients, of the consistency of treatment efficacy.

DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR.

PURPOSE: To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting. METHODS: Retrospective review of secondary MH surgeries. RESULTS: A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into this study with a mean MH size of 762 µ m and a mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.11 (∼20/260 Snellen). Closure rates were 89.3% for tissue transplantation, 77.3% for internal limiting membrane (ILM) flaps, 92.9% for MH manipulation, and 12.5% for repeat ILM peeling ( P < 0.05). Best-corrected visual acuity changes in logarithm of the minimum angle of resolution from baseline to postoperative month six were +0.29 for ILM peeling alone (15 Early Treatment Diabetic Retinopathy Study letters worse), -0.39 for MH manipulation (20 Early Treatment Diabetic Retinopathy Study letters improved), -0.23 for tissue transplantation (13 Early Treatment Diabetic Retinopathy Study letters improved), and -0.2 for ILM flaps (10 Early Treatment Diabetic Retinopathy Study letters improved; P < 0.05). CONCLUSION: Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of approximately 750 eyes.

Retinal Findings in Haemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts (HDBSCC): Case Report and Review.

We describe a child from a consanguineous family born with a rare autosomal recessive disorder affecting junctional adhesion molecule 3 (JAM3) causing profound neurological and ophthalmological injury known as haemorrhagic brain destruction, subependymal calcifications, and congenital cataracts (HDBSCC; MIM# 613730). She was the product of an unremarkable pregnancy and was born near to term but was noted shortly after birth to have congenital cataracts, poor vision, increased muscle tone, seizures, and developmental delay. Her older sister had an identical syndrome and had previously been documented to have homozygous mutations in JAM3. Examination in our patient, although difficult because of bilateral central cataracts, revealed very poor vision, attenuated retinal vessels, optic atrophy, and a retinal haemorrhage in the right eye, implying that abnormal development of the retinas and/or optic nerves may at times play a significant role in the poor vision noted in children with HDBSCC.

Subretinal Implantation of RPE on a Carrier in Minipigs: Guidelines for Preoperative Preparations, Surgical Techniques, and Postoperative Care.

Degenerative disorders of the retina (including age-related macular degeneration), which originate primarily at or within the retinal pigmented epithelial (RPE) layer, lead to a progressive disorganization of the retinal anatomy and the deterioration of visual function. The substitution of damaged RPE cells (RPEs) with in vitro cultured RPE cells using a subretinal cell carrier has shown potential for re-establishing the anatomical structure of the outer retinal layers and is, therefore, being further studied. Here, we present the principles of a surgical technique that allows for the effective subretinal transplantation of a cell carrier with cultivated RPEs into minipigs. The surgeries were performed under general anesthesia and included a standard lens-sparing three-port pars plana vitrectomy (PPV), subretinal application of a balanced salt solution (BSS), a 2.7 mm retinotomy, implantation of a nanofibrous cell carrier into the subretinal space through an additional 3.0 mm sclerotomy, fluid-air exchange (FAX), silicone oil tamponade, and closure of all the sclerotomies. This surgical approach was used in 29 surgeries (18 animals) over the past 8 years with a success rate of 93.1%. Anatomic verification of the surgical placement was carried out using in vivo fundus imaging (fundus photography and optical coherence tomography). The recommended surgical steps for the subretinal implantation of RPEs on a carrier in minipig eyes can be used in future preclinical studies using large-eye animal models.

Management of Diabetic Macular Edema: Guidelines from the Emirates Society of Ophthalmology.

In the United Arab Emirates, retinopathy has been shown to be present in 19% of the diabetic population, with diabetes identified in up to 40% of individuals aged over 55 years. Despite the prevalence of diabetic retinal diseases, there are no unified national guidelines on the management of diabetic macular edema (DME). These published guidelines are based on evidence taken from the literature and published trials of therapies, and consensus opinion of a representative expert panel with an interest in this condition, convened by the Emirates Society of Ophthalmology. The aim is to provide evidence-based, clinical guidance for the best management of different aspects of DME, with a special focus on vision-threatening diabetic retinopathy. Treatment should be initiated in patients with best-corrected visual acuity 20/30 or worse, and/or features of DME as seen on optical coherence tomography (OCT) with central retinal thickness (CRT) of at least 300 µm or in symptomatic patients with vision better than 20/25, and/or CRT less than 300 µm where there are OCT features consistent with center-involving macular edema. The treatment of DME is effective irrespective of glycated hemoglobin (HbA1c) level, and treatment must not be denied or delayed in order to optimize systemic parameters. All ophthalmic treatment options should be discussed with the patient for better compliance and expectations. Non-center-involving DME can be initially observed until progression toward the center is documented. Macular laser no longer has a primary role in center-involving DME, and anti-vascular endothelial growth factor (anti-VEGF) therapy should be considered as first-line treatment for all patients, unless contraindicated. If anti-VEGF is contraindicated, a steroid dexamethasone implant can be considered for first-line treatment. Recommendations for the treatment of DME in special circumstances and in relapsing and refractory DME are also discussed.

Novel retinal observations in a child with DiGeorge (22q11.2 deletion) syndrome.

Purpose: DiGeorge (22q11.2 deletion) syndrome is the most common human deletion syndrome with wide range of ocular manifestations. Herein we describe a case with novel retinal observations in this conditions. Observations: Retinal vascular dysplasia, peripapillary, intraretinal and vitreous hemorrhage were observed in a premature child with DiGeorge syndrome. Vitreous hemorrhage was treated with intravitreal injection of anti-angiogenicagents and pars plana vitrectomy surgery. Fundus fluorescein angiography did not confirm leakage of dye from dysplastic retinal vessels. Conclusions and Importance: Patients with DiGeorge syndrome may develop retinal vascular dysplasia, peripapillary, intraretinal and vitreous hemorrhage.