Radiation-Induced DNA Damage in Uveal Melanoma Is Influenced by Dose Delivery and Chromosome 3 Status.

Purpose: The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status. Methods: A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization. Results: The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05). Conclusions: Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.

The time course of spontaneous closure of idiopathic full-thickness macular holes.

PURPOSE: Spontaneous closure of idiopathic full-thickness macular holes (iFTMH) has been reported regularly. However, little is known about its probability and timeline. METHODS: In this retrospective study all consecutive patients who presented between August 2008 and August 2019 were screened for the presence of a macular hole and only iFTMHs were included. The primary outcome measure was the spontaneous closure of the iFTMH. RESULTS: Of 1256 eyes with macular holes, 338 fulfilled the inclusion criteria. Spontaneous closure of the iFTMH was detected in 31 eyes (9.2%) with a median time of 44 days after diagnosis. Eyes exhibiting spontaneous closure demonstrated a higher baseline best-corrected visual-acuity (BCVA) and smaller iFTMH diameter (p < 0.0001 and p < 0.0001, respectively). The mean BCVA improved from 0.4 logMAR (SD ± 0.21) to 0.29 logMAR (SD ± 0.20) after spontaneous closure (p = 0.031). The iFTMH diameter was positively correlated with the time to spontaneous closure (Pearson-r = 0.37, p = 0.0377). Spontaneously closed iFTMHs reopened in 16% (n = 5) of cases, with a median of 136 days after closure. A logistic regression model showed the hole diameter was associated with spontaneous closure (odds-Ratio 0.97, 95%CI [0.96, 0.98]). The Kaplan-Meier-Curve revealed that approximately 25% of small-iFTMH (n = 124) and 55% of iFTMH with a diameter < 150µm (n = 48) closed spontaneously within two months. CONCLUSION: The established gold-standard for the treatment of iFTMHs is macular surgery. However, the potential for spontaneous closure of small iFTMHs must be acknowledged. Therefore, if surgical treatment is delayed in individual cases, close observation is recommended.

[Surgical therapy and pathogen detection in endogenous endophthalmitis : Analysis of data from five German eye hospitals]. / Operative Therapie und Keimnachweis bei endogener Endophthalmitis : Datenauswertung aus 5 Augenkliniken.

BACKGROUND: Endogenous endophthalmitis results from hematogenous spread of bacterial or fungal infection in severely diseased patients. Specific systemic and intraocular therapy is required. The basis for this treatment is causal pathogen detection in blood culture or vitreous sample. However, functional results are limited. OBJECTIVE: The current article provides practical hints for surgical therapy and pathogen detection in patients with endogenous endophthalmitis. METHODS: A retrospective analysis of anonymous data of 68 male and female patients from 2018-2023 from five ophthalmology clinics in Germany was performed. RESULTS: Mean age of affected patients was 71.4 years (31-96 years). Surgical therapy included pars plana vitrectomy (ppV) and intravitreal injection (IVOM). In 44 of 68 patients (65%), 1-3 surgeries were performed, 4-6 surgeries were required in 14/68 (21%) of patients, and 10 or more surgeries were required in 4/68 patients (6%). Pathogen detection was possible in 34% of vitreous specimens and in 11% of anterior chamber samples. Mean initial visual acuity was logMAR 1.5. After treatment and a mean follow-up of 2.5 months, mean visual acuity was logMAR 1.3. Preanalytical methods for specimen collection like the Freiburg endophthalmitis set to optimize pathogen detection are presented. CONCLUSION: Severe inflammatory intraocular reactions in endogenous endophthalmitis necessitate a combination of ppV and repeated IVOM. In addition to providing a vitreous sample, ppV also serves to remove inflammatory fibrin membranes. Early pars plana vitrectomy with specific antibiotic or antifungal therapy should be sought in addition to the focus search and systemic therapy.

Fall-related ocular trauma in patients over 90 years in tertiary ophthalmic center in Germany: 90-TOSG Report 1.

PURPOSE: To investigate the clinical characteristics of fall-related ocular trauma in patients over 90 years of age. METHODS: Retrospective, medical record reviews. Patients over the age of 90 years treated in a tertiary center with fall-related ocular trauma were included in the study. RESULTS: Fifty consecutive patients (fifty eyes) were analyzed. The mean age was 93.6 ± 1.8 years and 41 patients (82%) were female. The most common site of the injuries was orbital fracture (18 patients, 36%), accompanied with open globe rupture (OGR) in three patients, and globe contusion in two patients. Seventeen patients (34%) presented with OGR. Ocular trauma score in those patients was category 1 in 10 patients (58.8%) and category 2 in the others. Conjunctival hemorrhage and/or periocular contusion was seen in 14 patients (28%) and globe contusion in six patients (12%). At the presentation, the mean best corrected visual acuity (BCVA) was 2.82 ± 0.24 logMAR in patients with OGR and 1.98 ± 0.81 logMAR in six patients with globe contusion. Three of the patients with OGR had a final vision of 20/200 or better whereas the remaining patients had hand movements or less. The most common risk factors were female gender (82%) and use of antihypertensive drugs (46%). CONCLUSION: Patients with OGR had a poor visual outcome despite the early treatment. It is important to raise public awareness about of the poor prognosis of ocular injuries due to falls in the elderly population in order to establish preventive measures.

A Case Study from the Past: "The RGC-5 vs. the 661W Cell Line: Similarities, Differences and Contradictions-Are They Really the Same?"

In the pursuit of identifying the underlying pathways of ocular diseases, the use of cell lines such as (retinal ganglion cell-5) RGC-5 and 661W became a valuable tool, including pathologies like retinal degeneration and glaucoma. In 2001, the establishment of the RGC-5 cell line marked a significant breakthrough in glaucoma research. Over time, however, concerns arose about the true nature of RGC-5 cells, with conflicting findings in the literature regarding their identity as retinal ganglion cells or photoreceptor-like cells. This study aimed to address the controversy surrounding the RGC-5 cell line's origin and properties by comparing it with the 661W cell line, a known cone photoreceptor model. Both cell lines were differentiated according to two prior published redifferentiation protocols under the same conditions using 500 nM of trichostatin A (TSA) and investigated for their morphological and neuronal marker properties. The results demonstrated that both cell lines are murine, and they exhibited distinct morphological and neuronal marker properties. Notably, the RGC-5 cells showed higher expression of the neuronal marker ß-III tubulin and increased Thy-1-mRNA compared with the 661W cells, providing evidence of their different properties. The findings emphasize the importance of verifying the authenticity of cell lines used in ocular research and highlight the risks of contamination and altered cell properties.

Two Methods for the Isolation and Cultivation of Porcine Primary Corneal Cells.

In ophthalmic research, there is a strong need for in vitro corneal cell models. Here, we describe different protocols for the cultivation of primary corneal cells that were isolated from porcine eyes. This primary cell culture can be used to test new therapeutic options for corneal diseases, such as dry eye disease, traumatic injuries, or corneal infections, and to study limbal epithelial stem cell (LESC) expansion. Two different isolation methods were performed: the outgrowth and the collagenase method. To perform the outgrowth protocol, small explants of the corneal limbus were generated and incubated in culture flasks in an incubator for 4-5 weeks. Regarding the collagenase method, to extract corneal cells, porcine corneas were removed, cut into small pieces, and incubated with collagenase. After incubation and centrifugation, the cells were seeded in 6- or 12-well plates and incubated in an incubator for 2-3 weeks. The differences between corneal cell cultivation with fetal bovine serum (FBS) and without it are also discussed. Therefore, the main advantages of the outgrowth method are that it requires fewer porcine eyes, and it takes less time to be performed compared to the collagenase method. On the other hand, with the collagenase method, mature cells are obtained earlier, at about 2 to 3 weeks.

Pupillotonia after endolaser retinopexy during vitrectomy for retinal detachment: a prospective cohort study comparing circumferential and focal retinopexy.

PURPOSE: To determine differences in postoperative pupil diameter in eyes that undergo pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) with endolaser retinopexy (ELR), comparing 360° vs focal ELR. METHODS: Patients with uncomplicated RRD who underwent PPV were prospectively analysed regarding the postoperative pupil diameter difference (PDD) between the affected eye and the partner eye. Group 1 underwent 360° ELR and group 2 received focal ELR. Postoperative vision and complications, including redetachment rate, macular oedema and epiretinal membrane formation, were also compared. RESULTS: A total of 72 patients, 42 in group 1 and 30 in group 2, were analysed. PDD, as observed at 6 weeks, was significantly greater than the preoperative values in both groups 1 and 2. It increased by a mean of 1±1.11 mm in group 1 and by 0.5±0.78 in group 2. This initial increase in PDD receded over time, but remained statistically significant in both groups, even at 6 months. The top 20% of patients with the largest PDD change comprised 13 out of 15 eyes from group 1, which was a statistically significant overrepresentation (p=0.0435). CONCLUSIONS: Moderate pupillotonia was induced post-ELR in vitrectomy and correlated to the extent of ELR. The pupillotonia effect of ELR was significantly less marked in pseudophakic eyes.

CLOUDING OF INTRAOCULAR SILICONE OIL IN THE ABSENCE OF EMULSIFICATION.

PURPOSE: To describe intraocular clouding of silicone oil in the absence of emulsification. METHODS: Retrospective observational case series of patients who received silicone oil injections and developed silicone oil discoloration without emulsification after pars plana vitrectomy. Clinical examinations and physicochemical analyses were performed to find out the common cause for the opaque oil. RESULTS: Thirteen patients developed silicone oil discoloration after pars plana vitrectomy. It could be traced down that all patients had received silicone oil from one respective production batch. The silicone oil was removed as soon as possible after the changes were detected (range, 8-16 weeks). Gas chromatography flame ionization detector, size exclusion chromatography, and high-performance liquid chromatography analysis showed the absence of low-molecular-weight compounds in the opaque lot. Thermogravimetric analysis revealed the opaque lot was more temperature stable. During the follow-ups, no obvious retinal toxicity could be observed and best-recorded visual acuity improved considerably in 12 patients and was only limited by the underlying retinal pathologic conditions. CONCLUSION: This is the first report on opacification of intraocular silicone oil without emulsification. This discoloration of silicone oil may disturb vision and prevent proper fundus examination; however, it seems to be a nontoxic phenomenon without serious long-term consequences.

Porcine Corneas Incubated at Low Humidity Present Characteristic Features Found in Dry Eye Disease.

Dry eye is a multifactorial disease that affects the ocular surface and tear fluid. Current treatment options include lubricant eye drop application several times a day. However, these eye drops often cause local side effects like ocular allergies or blurred vision after the application. To test new treatment options, a robust dry eye model is needed. Here, a porcine ex vivo model was established by means of incubation of porcine corneas in low humidity (LH) and characterized by histological damage evaluation, epithelial thickness and by relevant dry eye markers, such as interleukin 1 beta (IL-1ß), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), occludin and galectin-3. In the dry eye model proposed, an increased secretion of IL-1ß was observed, as well as an upregulation of NF-κB, occludin and galectin-3 mRNA expression. Moreover, the model presented a higher rate of cell death in comparison to the controls. These effects could be reversed with successful treatment of dexamethasone (dexa) and partially reversed with hyaluronic acid (HA) containing eye drops. Furthermore, medium-molecular-weight HA stimulated an increase in IL-1ß in the model proposed. In conclusion, this dry eye model mimics the in vivo condition and hence allows for animal-free testing of novel dry eye treatments.

Analysis of retinal detachment resulted from post-operative endophthalmitis treated with 23G pars Plana Vitrectomy.

BACKGROUND: To evaluate the rate, risk factors, functional outcome and prognosis in eyes with retinal detachment after post-operative endophthalmitis treated with 23G Pars Plana Vitrectomy. METHODS: Electronic patient files from 2009 until 2018 were screened for the presence of an endophthalmitis. Included were 116 eyes of 116 patients. This population was evaluated for the rate of retinal detachment after 23G Pars Plana Vitrectomy for endophthalmitis following cataract surgery or intravitreal injection. The main outcome measures were retinal detachment and visual acuity. RESULTS: The reasons for endophthalmitis were previous cataract surgery in 78 patients and following intravitreal injection in 38 patients. The first clinical evidence of endophthalmitis was present in median 5 days after the triggering intervention. Twenty-five eyes (21.55%) developed a retinal detachment an average of 25 days after endophthalmitis. RD is significantly associated with preoperative visual acuity (p = 0.001). CONCLUSIONS: We emphasize the prognostic role of preoperative visual acuity in RD development of the endophthalmitis treated with 23G Pars Plana Vitrectomy.

Cyclosporine A Protects Retinal Explants against Hypoxia.

The retina is a complex neurological tissue and is extremely sensitive to an insufficient supply of oxygen. Hypoxia plays a major role in several retinal diseases, and often results in the loss of cells that are essential for vision. Cyclosporine A (CsA) is a widely used immunosuppressive drug. Furthermore, treatment with CsA has neuroprotective effects in several neurologic disorders. No data are currently available on the tolerated concentration of CsA when applied to the retina. To reveal the most effective dose, retinal explants from rat eyes were exposed to different CsA concentrations (1-9 µg/mL). Immunohistochemistry with brain-specific homeobox/POU domain protein 3a (Brn3a) and TUNEL staining was performed to determine the percentage of total and apoptotic retinal ganglion cells (RGCs), as well as the responses of micro- and macroglial cells. Furthermore, optical coherence tomography (OCT) scans were performed to measure the changes in retinal thickness, and recordings with multielectrode array (MEA) were performed to evaluate spontaneous RGC spiking. To examine the neuroprotective effects, retinas were subjected to a hypoxic insult by placing them in a nitrogen-streamed hypoxic chamber prior to CsA treatment. In the biocompatibility tests, the different CsA concentrations had no negative effect on RGCs and microglia. Neuroprotective effects after a hypoxic insult on RGCs was demonstrated at a concentration of 9 µg/mL CsA. CsA counteracted the hypoxia-induced loss of RGCs, reduced the percentage of TUNEL+ RGCs, and prevented a decrease in retinal thickness. Taken together, the results of this study suggest that CsA can effectively protect RGCs from hypoxia, and the administered concentrations were well tolerated. Further in vivo studies are needed to determine whether local CsA treatment may be a suitable option for hypoxic retinal diseases.

High-addition segmented refractive bifocal intraocular lens in inactive age-related macular degeneration: A multicenter pilot study.

This multicenter, open-label study aimed to determine the safety and functional outcome of a high-addition segmented refractive bifocal intraocular lens (IOL) in late inactive age-related macular degeneration (AMD). Twenty eyes of 20 patients were enrolled and followed until 12 months after the intervention. Patients underwent cataract surgery with implantation of a LS-313 MF80 segmented refractive bifocal intraocular lens with a near addition of +8.0 D (Teleon Surgical Vertriebs GmbH, Berlin, Germany). The main outcome measures were distance corrected near visual acuity (DCNVA) and safety as determined by intra- and post-operative complications. Secondary outcomes included distance corrected visual acuity (CDVA), uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), the need for magnification to read newspaper, preferred reading distance, speed and performance (logRAD), as well as patient satisfaction. Mean DCNVA improved from 0.95 (±0.19) to 0.74 (±0.35) logMAR, until 6 months after surgery, P<0.05. CDVA improved from 0.70 (±0.23) to 0.59 (±0.30) logMAR, UDVA from 0.94 (±0.25) to 0.69 (±0.34) logMAR, UNVA from 1.08 (±0.19) to 0.87 (±0.43) logMAR. The mean need for magnification decreased from 2.9- to 2.3-fold, preferred reading distance from 23 to 20 cm. No intraoperative complications occurred during any of the surgeries. One patient lost > 2 lines of CDVA between 6 and 12 months, in another case, the study IOL was exchanged for a monofocal one due to dysphotopsia and decreased CDVA. Implantation of a segmented refractive bifocal IOL with +8.0 D addition improves near and distance vision in patients with late AMD and has a satisfactory safety profile.

CT Assessment of Intraorbital Cable Movement of Electronic Subretinal Prosthesis in Three Different Surgical Approaches.

Purpose: Electronic retinal implants restore some visual perception in patients blind from retinitis pigmentosa. Eye movements cause mechanical stress in intraorbital power supply cables leading to cable breaks. By using computer tomography (CT) scans at the extreme positions of the four cardinal gaze directions, this study determined in vivo, which of three surgical routing techniques results in minimal bending radius variation and favors durability. Methods: Nine patients received the first-generation subretinal implant Alpha IMS (Retina Implant AG, Reutlingen, Germany) in one eye. Three techniques for intraorbital cable routing were used (straight cable route (A), parabulbar loop (B), and encircling band (C)), each in three patients. All patients underwent computer tomography of the orbital region. The bending radius of the intraorbital cable was measured with the DICOM viewer Osirix v4.1.2 (Pixmeo SARL, Bernex, Switzerland) and served as indicator for mechanical stress. Results: Average bending radius variation was 87% for method A, 11% for method B, and 16% for method C. Methods A and B (P = 0.005) and methods A and C (P = 0.007) differed significantly, while method B and C showed no statistical difference (P = 0.07). Conclusions: Compared to straight routes, arcuated cable routes significantly reduce cable movement and bending. Due to an easier surgical procedure, a parabulbar loop is the preferred method to minimize bending radius variation and prolong survival time of electronic subretinal implants. Translational Relevance: CT analysis of cable bending of implanted medical devices allows to determine which surgical routing technique favors durability in vivo.

Improved Treatment Options for Glaucoma with Brimonidine-Loaded Lipid DNA Nanoparticles.

Glaucoma is the second leading cause of irreversible blindness worldwide. Among others, elevated intraocular pressure (IOP) is one of the hallmarks of the disease. Antiglaucoma drugs such as brimonidine can lower the IOP but their adherence to the ocular surface is low, leading to a low drug uptake. This results in a frequent dropping regime causing low compliance by the patients. Lipid DNA nanoparticles (NPs) have the intrinsic ability to bind to the ocular surface and can be loaded with different drugs. Here, we report DNA NPs functionalized for loading of brimonidine through specific aptamers and via hydrophobic interactions with double stranded micelles. Both NP systems exhibited improved affinity toward the cornea and retained release of the drug as compared to controls both in vitro and in vivo. Both NP types were able to lower the IOP in living animals significantly more than pristine brimonidine. Importantly, the brimonidine-loaded NPs showed no toxicity and improved efficacy and hence should improve compliance. In conclusion, this drug-delivery system offers high chances of an improved treatment for glaucoma and thus preserving vision in the aging population.

Comparison of spherical and aspherical intraocular lenses with decentration and tilt error using a physical model of human contrast vision and an image quality metric.

PURPOSE: In this study, two intraocular lenses (spherical IOL SA60AT and aspherical IOL SN60WF) are examined in an eye model under conditions of misalignment (defocus, decentration and tilt). The lenses are rated using the contrast sensitivity function (CSF) based on Barten's physical model. The square root integral (SQRI) method is used as a quality criterion comparable to the subjective image quality assessment of the human eye. METHODS: The IOLs to be tested are decentered from 0 to 1mm and tilted from -5 to +5 degrees in the Navarro eye model (optimized for far-point 6m and pupil aperture 3mm). The defocus of the IOLs is ±0.1mm at the anterior chamber depth (ACD). The optical modulation transfer function (MTF) is simulated with a ray tracing program. The SQRI is calculated using this MTF and the Barten CSF model (for in-focus at aperture 3 and 4.5mm and for defocus at 3mm). RESULTS: With increasing decentration, the spherical IOL shows a significantly smaller loss of quality for both apertures compared to the aspherical lens. With an aperture of 4.5mm, the image quality of the aspherical IOL is better for small decentration and tilt. The loss of quality of the spherical IOL increases with increasing tilt in both directions. In contrast, the image quality of the aspherical IOL is reduced under decentration for certain tilt values. For ACD-0.1mm, both IOLs behave similarly to the in-focus situation. For ACD+0.1mm, the influence of tilt without decentration is small for both IOLs. With increasing decentration, the quality loss of the aspherical IOL is similar to that in-focus and greater than that of the spherical lens. CONCLUSION: In general, under the same conditions the spherical SA60AT displays a lower tolerance in loss of quality of subjective vision with lens alignment errors, in comparison to the aspherical SN60WF, limited by certain combinations of decentration and tilt according to this study. This study shows a way to evaluate IOLs based on the subjective visual performance of the eye.

Self-assembled DNA nanoparticles loaded with travoprost for glaucoma-treatment.

Lipid DNA nanoparticles (NPs) exhibit an intrinsic affinity to the ocular surface and can be loaded by hybridization with fluorophore-DNA conjugates or with the anti-glaucoma drug travoprost by hybridizing an aptamer that binds the medication. In the travoprost-loaded NPs (Trav-NPs), the drug is bound by specific, non-covalent interactions, not requiring any chemical modification of the active pharmaceutical ingredient. Fluorescently labeled Trav-NPs show a long-lasting adherence to the eye, up to sixty minutes after eye drop instillation. Biosafety of the Trav-NPs was proved and in vivo. Ex vivo and in vivo quantification of travoprost via LC-MS revealed that Trav-NPs deliver at least twice the amount of the drug at every time-point investigated compared to the pristine drug. The data successfully show the applicability of a DNA-based drug delivery system in the field of ophthalmology for the treatment of a major retinal eye disease, i.e. glaucoma.

Restriction of eye motility in patients with RETINA IMPLANT Alpha AMS.

PURPOSE: To evaluate the motility of the eye in patients with the RETINA IMPLANT Alpha AMS. METHODS: Eye motility was determined in eight gaze directions in ten blind retinitis pigmentosa patients, who had received the RETINA IMPLANT Alpha AMS, before implantation of the subretinal implant and at six time-points up to one year after. RESULTS: The analysis of eye motility showed a restriction in the upgaze and gaze to the temporal side directly after surgery in eight of the nine patients included. The degree of motility restriction decreased continuously with recovery during the observation time. One year after surgery, eye motility was still restricted in the majority of patients, especially in the upgaze to the temporal side at 20° (five of seven patients). CONCLUSION: Retinal implants with intraorbital parts (e.g. connecting cables) caused restriction in the temporal and superior viewing directions in the majority of patients. Although this restriction might be cosmetically visible, this limitation in eye motility has no effects on the monocular vision and the implant's efficacy for daily use.

CHANGES IN RETINAL SENSITIVITY AFTER GENE THERAPY IN CHOROIDEREMIA.

PURPOSE: Choroideremia (CHM) is a rare inherited retinal degeneration resulting from mutation of the CHM gene, which results in absence of functional Rab escort protein 1 (REP1). We evaluated retinal gene therapy with an adeno-associated virus vector that used to deliver a functional version of the CHM gene (AAV2-REP1). METHODS: THOR (NCT02671539) is a Phase 2, open-label, single-center, randomized study. Six male patients (51-60 years) with CHM received AAV2-REP1, by a single 0.1-mL subretinal injection of 10 genome particles during vitrectomy. Twelve-month data are reported. RESULTS: In study eyes, 4 patients experienced minor changes in best-corrected visual acuity (-4 to +1 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); one gained 17 letters and another lost 14 letters. Control eyes had changes of -2 to +4 letters. In 5/6 patients, improvements in mean (95% confidence intervals) retinal sensitivity (2.3 [4.0] dB), peak retinal sensitivity (2.8 [3.5] dB), and gaze fixation area (-36.1 [66.9] deg) were recorded. Changes in anatomical endpoints were similar between study and control eyes. Adverse events were consistent with the surgical procedure. CONCLUSION: Gene therapy with AAV2-REP1 can maintain, and in some cases, improve, visual acuity in CHM. Longer term follow-up is required to establish whether these benefits are maintained.