Retinal and choroidal efficacy of switching treatment to faricimab in recalcitrant neovascular age related macular degeneration.

Aim of this study was to evaluate the efficacy of switching treatment to faricimab in neovascular age-related macular degeneration (nAMD) from other anti-VEGF agents. Fifty-eight eyes of fifty-one patients with nAMD and a full upload series of four faricimab injections were included. Demographic data, multimodal imaging and treatment parameters were recorded. The primary outcome measures were changes in central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). A subgroup analysis was performed for eyes with prior ranibizumab (R) or aflibercept (A) treatment. Mean injection intervals before and after switching were comparable (33.8 ± 11.2 vs. 29.3 ± 2.6 days; p = 0.08). Mean CST of 361.4 ± 108.1 µm prior to switching decreased significantly to 318.3 ± 97.7 µm (p < 0.01) after the third faricimab injection, regardless of prior anti-VEGF treatment (p < 0.01). Although SFCT slightly improved for the whole cohort from 165.8 ± 76.8 µm to 161.0 ± 82,8 µm (p = 0.029), subgroup analysis did not confirm this positive effect (subgroup R: p = 0.604; subgroup A: p = 0.306). In patients with a suboptimal response to aflibercept or ranibizumab in nAMD, farcimab can improve CST and slightly improve or maintain SFCT. Further prospective randomized trials are warranted.

[Selective vital dyes in macular surgery : Do they increase the probability of intraoperative identification of the internal limiting membrane also for an experienced surgeon?] / Selektive Vitalfarbstoffe in der Makulachirurgie : Erhöhen sie die Wahrscheinlichkeit der intraoperativen ILM-Identifizierung auch bei einem erfahrenen Operateur?

BACKGROUND: Various vital dyes exist on the market for intraoperative internal limiting membrane (ILM) identification. The aim of this study was to verify the added value of these dyes for ILM identification and in the difficulty of ILM peeling during pars plana vitrectomy (ppV) by a single surgeon highly experienced in this operation. MATERIAL AND METHODS: In this study 400 ppV surgical reports involving ILM peeling were retrospectively analyzed. Intraoperative assessment of identification or difficulty of intraoperative ILM peeling had to be documented in the surgical report. The total group consisted of 2 cohorts each with 200 surgical reports (first cohort without selective vital dyes, period 2004-2006; second cohort with vital dyes in the majority of ppVs, period 2013-2020). RESULTS: The difference between both groups in terms of intraoperative identification of ILM was statistically significant (p < 0.001); however, no statistically significant difference (p = 0.951) was found between the two groups in terms of difficulty of ILM peeling. In logistic regression analysis neither patient gender, age, eye side, lens status nor posterior vitreous limiting membrane status were significantly associated with ILM identification. CONCLUSION: The introduction of intravital dyes represents a decisive advancement in retinal surgery. In the investigated sample this benefit was evident from two precisely defined surgical cohorts of a single highly experienced surgeon. This underlines the additional benefit of using selective vital dyes to identify ILM in macular surgery for less experienced surgeons.

Optimizing Refractive Outcomes of SMILE: Artificial Intelligence versus Conventional State-of-the-Art Nomograms.

PURPOSE: AI (artificial intelligence)-based methodologies have become established tools for researchers and physicians in the entire field of ophthalmology. However, the potential of AI to optimize the refractive outcome of keratorefractive surgery by means of machine learning (ML)-based nomograms has not been exhausted yet. In this study, we wanted to comprehensively compare state-of-the-art conventional nomograms for Small-Incision-Lenticule-Extraction (SMILE) with a novel ML-based nomogram regarding both their spherical and astigmatic predictability. METHODS: A total of 1,342 eyes were analyzed for creation of three different nomograms based on a linear model (LM), a generalized additive mixed model (GAMM) and an artificial-neuronal-network (ANN), respectively. A total of 16 patient- and treatment-related features were included. Each model was trained by 895 eyes and validated by the remaining 447 eyes. Predictability was assessed by the difference between attempted and achieved change in spherical equivalent (SE) and the difference between target induced astigmatism (TIA) and surgically induced astigmatism (SIA). The root mean squared error (RMSE) of each model was computed as a measure of overall model performance. RESULTS: The RMSE of LM, GAMM and ANN were 0.355, 0.348 and 0.367 for the prediction of SE and 0.279, 0.278 and 0.290 for the astigmatic correction, respectively. By applying the created models, the theoretical yield of eyes within ±0.50 D of SE from target refraction improved from 82 to 83% (LM), 84% (GAMM) and 83% (ANN), respectively. Astigmatic outcomes showed an improvement of eyes within ±0.50 D from TIA from 90 to 93% (LM), 93% (GAMM) and 92% (ANN), respectively. Subjective manifest refraction was the single most influential covariate in all models. CONCLUSION: Machine learning endorsed the validity of state-of-the-art linear and non-linear SMILE nomograms. However, improving the accuracy of subjective manifest refraction seems warranted for optimizing ±0.50 D SE predictability beyond an apparent methodological 90% limit.

Risk of transient vision loss after intravitreal aflibercept using vial-prepared vs. the novel prefilled syringe formulation.

Purpose: To compare the risk of transient vision loss (TVL) probably attributable to a severe intraocular pressure spike after intravitreal aflibercept application using the novel prefilled syringe (PFS) vs. the established vial system (VS). Methods: Datasets of the intravitreal injection service of the Ludwig Maximilians-University Munich and the Technical University Munich, Germany, were screened for documentation of TVL after intravitreal injection of aflibercept. The observation period included two full months prior to the introduction of the novel PFS and two months afterwards. TVL was defined as loss of perception of hand motion for a duration of >30 s. Results: Over a period of four months, 1720 intravitreal injections of aflibercept were administered in 672 patients. There were 842 injections with the old VS, and 878 injections using the novel PFS. Using the VS, TVL was noted during two injections (0.24%) in two patients, as compared to 11 cases of TVL (1.25%) in 10 patients with the PFS (p = 0.015). Using the PFS, patients had a 5.3-fold risk of TVL as compared to the VS (OR: 5.33; 95% CI: 1.2-24.1; p = 0.0298). Conclusion: There was a more than five-fold risk of TVL using the novel pre-filled aflibercept syringe as compared to the established vial system. During informed consent, this risk should be discussed.

Assessment of ChatGPT in the Prehospital Management of Ophthalmological Emergencies - An Analysis of 10 Fictional Case Vignettes.

BACKGROUND: The artificial intelligence (AI)-based platform ChatGPT (Chat Generative Pre-Trained Transformer, OpenAI LP, San Francisco, CA, USA) has gained impressive popularity in recent months. Its performance on case vignettes of general medical (non-ophthalmological) emergencies has been assessed - with very encouraging results. The purpose of this study was to assess the performance of ChatGPT on ophthalmological emergency case vignettes in terms of the main outcome measures triage accuracy, appropriateness of recommended prehospital measures, and overall potential to inflict harm to the user/patient. METHODS: We wrote ten short, fictional case vignettes describing different acute ophthalmological symptoms. Each vignette was entered into ChatGPT five times with the same wording and following a standardized interaction pathway. The answers were analyzed following a systematic approach. RESULTS: We observed a triage accuracy of 93.6%. Most answers contained only appropriate recommendations for prehospital measures. However, an overall potential to inflict harm to users/patients was present in 32% of answers. CONCLUSION: ChatGPT should presently not be used as a stand-alone primary source of information about acute ophthalmological symptoms. As AI continues to evolve, its safety and efficacy in the prehospital management of ophthalmological emergencies has to be reassessed regularly.

Age-dependent retinal neuroaxonal degeneration in children and adolescents with Leber hereditary optic neuropathy under idebenone therapy.

BACKGROUND: The aim of this study was to investigate the neuroretinal structure of young patients with Leber hereditary optic neuropathy (LHON). METHODS: For this retrospective cross-sectional analysis, the peripapillary retinal nerve fiber layer (pRNFL) thickness and the macular retinal layer volumes were measured by optical coherence tomography. Patients aged 12 years or younger at disease onset were assigned to the childhood-onset (ChO) group and those aged 13-16 years to the early teenage-onset (eTO) group. All patients received treatment with idebenone. The same measurements were repeated in age-matched control groups with healthy subjects. RESULTS: The ChO group included 11 patients (21 eyes) and the eTO group 14 patients (27 eyes). Mean age at onset was 8.6 ± 2.7 years in the ChO group and 14.8 ± 1.0 years in the eTO group. Mean best-corrected visual acuity was 0.65 ± 0.52 logMAR in the ChO group and 1.60 ± 0. 51 logMAR in the eTO group (p < 0.001). Reduced pRNFL was evident in the eTO group compared to the ChO group (46.0 ± 12.7 µm vs. 56.0 ± 14.5 µm, p = 0.015). Additionally, a significantly lower combined ganglion cell and inner plexiform layer volume was found in the eTO compared to the ChO group (0.266 ± 0.0027 mm3 vs. 0.294 ± 0.033 mm3 , p = 0.003). No difference in these parameters was evident between the age-matched control groups. CONCLUSION: Less neuroaxonal tissue degeneration was observed in ChO LHON than in eTO LHON, a finding that may explain the better functional outcome of ChO LHON.

Optical coherence tomography-based misdiagnosis and morphological distinction in pachychoroid neovasculopathy vs. polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the rate of misdiagnosis of aneurysmatic pachychoroid type 1 choroidal neovascularization/polypoidal choroidal vasculopathy (PAT1/PCV) among cases diagnosed as non-aneurysmatic pachychoroid neovasculopathy (PNV) and to define optical coherence tomography (OCT) features facilitating their distinction. METHODS: The database of the Department of Ophthalmology, Ludwig-Maximilians University Munich, was screened for patients diagnosed with PNV. Multimodal imaging was screened for the presence of choroidal neovascularization (CNV) and aneurysms/polyps. Imaging features facilitating the diagnosis of PAT1/PCV were analysed. RESULTS: In total, 49 eyes of 44 patients with a clinical PNV diagnosis were included, of which 42 (85.7%) had PNV and 7 (14.3%) represented misdiagnosed PAT1/PCV. SFCT was comparable (PNV: 377 ± 92 vs. PAT1/PCV: 400 ± 83 µm; p = 0.39). Whereas no difference was detected in total pigment epithelium detachment (PED) diameter (p = 0.46), maximum PED height was significantly higher in the PAT1/PCV group (199 ± 31 vs. 82 ± 46, p < 0.00001). In a receiver operating characteristic (ROC) analysis, the optimum cutoff for defining "peaking PED" was 158 µm with an area under the curve of 0.969, a sensitivity of 1.0 (95% CI: 0.59-1.0), and a specificity of 0.95 (95% CI: 0.84-0.99). Sub-retinal hyperreflective material (SHRM; p = 0.04), sub-retinal ring-like structures (SRRLS; p < 0.00001), and sub-RPE fluid (p = 0.04) were significantly more frequent in eyes with PAT1/PCV. CONCLUSION: A relevant percentage of eyes diagnosed with PNV might instead suffer from PAT1/PCV. The detection of a maximum PED height ("peaking PED") exceeding approximately 150 µm, SHRM, SRRLS, and sub-RPE fluid might greatly aid in the production of a more accurate diagnosis.

Scleral Thickness as a Risk Factor for Central Serous Chorioretinopathy and Pachychoroid Neovasculopathy.

In the pathophysiology of central serous chorioretinopathy (CSC), scleral changes inducing increased venous outflow resistance are hypothesized to be involved. This work aims to investigate anterior scleral thickness (AST) as a risk factor for pachychoroid disorders. A randomized prospective case-control study was performed at the Ludwig Maximilians University, Department of Ophthalmology. In patients with CSC or pachychoroid neovasculopathy (PNV) and in an age- and refraction-matched control group, swept source optical coherence tomography (SS-OCT) was used to measure anterior scleral thickness (AST). Subfoveal choroidal thickness (SFCT) was assessed using enhanced depth imaging OCT (EDI-OCT). In total, 46 eyes of 46 patients were included in this study, with 23 eyes in the CSC/PNV and 23 eyes in the control group. A significantly higher AST was found in the CSC/PNV compared with the control group (403.5 ± 68.6 (278 to 619) vs. 362.5 ± 62.6 (218 to 498) µm; p = 0.028). Moreover, the CSC/PNV group showed a higher SFCT (392.8 ± 92.8 (191-523) vs. 330.95 ± 116.5 (167-609) µm, p = 0.004). Compared with the age- and refraction-matched controls, patients with CSC and PNV showed a significantly thicker anterior sclera. Scleral thickness might contribute to the venous overload hypothesized to induce pachychoroid phenotypes.

Long-Term Results of Adjunct Autologous Platelet-Rich Plasma in Lamellar Macular Hole Surgery Showing Lasting Restoration of Foveal Anatomy.

The aim of this study was to evaluate the long-time results of highly concentrated autologous platelet-rich plasma (PRP) used as an adjunct in lamellar macular hole (LMH) surgery. Nineteen eyes of nineteen patients with progressive LMH were enrolled in this interventional case series, on which 23/25-gauge pars plana vitrectomy was performed and 0.1 mL of highly concentrated autologous platelet-rich plasma was applied under air tamponade. Posterior vitreous detachment was induced, and the peeling of tractive epiretinal membranes, whenever present, was performed. In cases of phakic lens status, combined surgery was carried out. Postoperatively, all patients were instructed to remain in a supine position for the first two postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, and spectral domain optical coherence tomography (SD-OCT) were carried out preoperatively and at minimum 6 months (in median 12 months) postoperatively. Foveal configuration was postoperatively restored in 19 of 19 patients. Two patients who had not undergone ILM peeling showed a recurring defect at 6-month follow-up. Best-corrected visual acuity improved significantly from 0.29 ± 0.08 to 0.14 ± 0.13 logMAR (p = 0.028, Wilcoxon signed-rank test). Microperimetry remained unchanged (23.38 ± 2.53 preoperatively; 23.0 ± 2.49 dB postoperatively; p = 0.67). No patients experienced vision loss after surgery, and no significant intra- or postoperative complications were observed. Using PRP as an adjunct in macular hole surgery significantly improves morphological and functional outcomes. Additionally, it might be an effective prophylaxis to further progression and also the formation of a secondary full-thickness macular hole. The results of this study might contribute to a paradigm shift in macular hole surgery towards early intervention.

Childhood versus early-teenage onset Leber's hereditary optic neuropathy: visual prognosis and capacity for recovery.

OBJECTIVE: In Leber's hereditary optic neuropathy (LHON) in children and teenagers, the influence of age on visual prognosis has not yet been investigated. METHODS: Patients from the mitoNET registry with LHON onset at age 4-16 years with at least 4 years of follow-up without treatment were included. Visual acuity (VA) at baseline, lowest VA ever recorded (nadir) and VA at end of follow-up were compared between childhood onset (ChO, ≤12 years of age) and early-teenage onset (eTO; 13-16 years). RESULTS: Out of 231 patients with LHON, 19 met the inclusion criteria (8.2%). There were 11 patients in the ChO and 8 patients in the eTO group. Mean age at onset was 8.6 (SD 2.1) years (ChO) and 15.4 (SD 0.7) years (eTO) (p<0.00001). Follow-up was mean 184 (SD 129) months (ChO) and 119 (SD 78) months (eTO) (p=0.22). Baseline VA was similar between both groups in better (p=0.96) and worse eyes (p=0.54). In worse eyes, both groups deteriorated similarly (p=0.79) until nadir and showed similar recovery until end of follow-up (p=0.38). In better eyes, both groups deteriorated similarly (p=0.16) until nadir. From nadir until end of follow-up, better eyes in the ChO group showed a significantly better recovery (-0.35 (SD 0.36) vs -0.01 (SD 0.06) logMAR; p=0.02) than eTO eyes. CONCLUSION: Visual prognosis of LHON in children is much more favourable in cases of childhood onset (≤12 years of age) as compared with teenage onset (13-16 years), mostly due to better recovery from nadir in childhood onset.

How should we report the foveal status in eyes with "macula-off" retinal detachment?

Whilst pre- and postoperative multimodal imaging technologies including optical coherence tomography (OCT) have investigated the morphological correlates of worsened visual outcomes in rhegmatogenous retinal detachment (RRD) with foveal involvement, the nomenclature has adhered to the traditional ophthalmoscopy-based and rather vague term "macula-off". This article appraises the current literature with regard to the preoperative assessment and nomenclature of the foveal status in macula involving retinal detachment (MIRD). A literature review of recent publications assessing functional or morphological outcomes in MIRD was conducted, using the search terms "fovea-off" or "macula-off". The search date was April 28th, 2021. Original studies in English language were included. Case reports, review articles or letters were excluded. Forty relevant articles (range of publication dates: July 29th, 2020 - April 18th, 2021) were reviewed to assess the diagnostic modalities used, morphological parameters assessed, and any specific nomenclature introduced to specify the extent of macular detachment. The results suggest widespread variability and inconsistencies with regard to the preoperative assessment, diagnostic modalities and nomenclature used to describe the foveal status in eyes with RRD termed "macula-off". The extent of macular detachment may be classified by a wide range of morphological parameters, including the height of foveal detachment and the ETDRS grid as overlay tool in OCT devices. There is a scientific and clinical need for an updated nomenclature for eyes with "macula-off" RRD. Preoperative OCT findings should be reported on a regular and standardized basis in order to establish a consensus how to report the foveal status in eyes with MIRD.

[Biomarkers in the treatment of retinal vein occlusion]. / Biomarker in der Therapie venöser retinaler Gefäßverschlüsse.

BACKGROUND: Retinal vein occlusion, subdivided into central retinal and branch retinal vein occlusion, is one of the most frequent vascular diseases of the retina. Biomarkers of optical coherence tomography (OCT), OCT-angiography and (ultra-widefield) fluorescein angiography are of exceptional importance in the initial diagnosis and also in the treatment of complications associated with retinal vascular occlusion, particularly macular edema. METHODS: A systematic literature review was carried out in PubMed with the keywords central retinal vein occlusion, branch retinal vein occlusion, biomarker, OCT, OCT angiography, ultra-widefield fluorescein angiography with prioritization of the most important aspects. RESULTS: Relevant biomarkers in OCT include central retinal thickness (CRT), macular fluid, the integrity of the photoreceptor bands (external limiting membrane and ellipsoid zone), disorganization of retinal inner layers (DRIL), hyperreflective foci, choroidal thickness and signs of ischemia, such as a prominent middle limiting membrane (p-MLM), paracentral acute middle maculopathy (PAMM) as well as hyperreflectivity of inner retinal layers (HIRL). The importance of OCT-angiography lies particularly in the assessment of microvascular alterations, especially vessel density in the deep retinal vascular plexus, the foveal avascular zone and of areas with no capillary perfusion. Biomarkers of ultra-widefield angiography, such as peripheral ischemia (ischemic index) and neovascularízation are essential with respect to treatment decisions for retinal laser. CONCLUSION: A multitude of simple and complex biomarkers currently enable an effective individualized evaluation of treatment and prognosis in retinal vein occlusion. A shift from invasive to noninvasive biomarkers can be observed.

Corneal Collagen Crosslinking (CXL) for Corneal Ectasia after Small Incision Lenticule Extraction (SMILE). / Korneales Kollagen-Crosslinking (CXL) bei Hornhautektasie nach SMILE (Small Incision Lenticule Extraction).

With an estimated incidence of 0.011%, the SMILE procedure seems to have the lowest risk of postoperative keratectasia among contemporary keratorefractive procedures. Nevertheless, due to the novelty of the procedure as well as the lack of data, no clear superiority over femto-LASIK or PRK can be stated at this time. In this respect, application of the identical tomographic screening criteria previously developed for excimer-based procedures is of paramount importance to minimize the risk of corneal ectasia. As an adjunct to conventional corneal tomography, newer imaging modalities such as OCT-based epithelial mapping should be used for preoperative screening before keratorefractive surgery. Corneal crosslinking is an established treatment modality for post-SMILE keratectasia, which promises high success rates especially in early stages. The present case report illustrates these diagnostic and therapeutic considerations.

[Phototherapeutic keratectomy for recurrent corneal erosion of various epithelial origins: influence of depth of ablation on pachymetry and refraction]. / Phototherapeutische Keratektomie bei rezidivierenden Hornhauterosionen verschiedener epithelialer Genese: Einfluss der Ablationstiefe auf Pachymetrie und Refraktion.

BACKGROUND: Phototherapeutic keratectomy (PTK) is an established treatment method for patients suffering from either genetic corneal dystrophy or recurrent corneal erosion (RCE) without underlying basement membrane dystrophy, often caused by trauma. OBJECTIVE: This study aimed to describe the changes in manifest subjective refraction and pachymetry after PTK treatment in patients suffering from epithelial basement membrane dystrophy (EBMD) and traumatic or atraumatic RCE without underlying EBMD. MATERIAL AND METHODS: This was a retrospective, single-center study performed at the Department of Ophthalmology of the Ludwig-Maximilians University (Munich). Patient data were retrospective collected using the smart-eye database of the Department of Ophthalmology including diagnostic data from an autorefractometer and from the Pentacam HR. All laser treatments were performed with an ablation depth of 10 µm for EBMD patients and 6 µm for RCE patients without EBMD. RESULTS: Both collectives showed a decrease in pachymetry larger than the calculated ablation depths after a follow-up interval of 126 days (95% CI 104-147 days). While the EBMD collective receiving an ablation of 10 µm showed a decrease of 25.8 µm (N = 74; 95% CI 21.2-30.3; p < 0.001), the non-EBMD collective receiving an ablation of 6 µm showed a decrease of 12.3 µm (N = 44, 95% CI 7.0-17.7; p < 0.001). Both, total corneal refractive power (TCRP) as well as spherical equivalent (SE) offered no significant change in preoperative and postoperative comparison for the EBMD collective. On the other hand, patients without underlying EBMD showed a significant myopic decrease in SE of 0.4 dpt (±0.7 dpt SD, p < 0.05). The mean follow-up interval was 126 days (95% CI 104-147 days). CONCLUSION: PTK treatment offers an effective method for patients suffering from either EBMD dystrophy or RCE syndrome without underlying EBMD. The final ablation based on pachymetry at the apex can be estimated at 2.3 to 2.6 times higher compared to the original ablation depth. The reasons for this are on the one hand the laser ablation itself and the influence of the reactive wound healing of the corneal epithelium.

Determinants of Subjective Quality of Vision After Phakic Intraocular Lens Implantation.

PURPOSE: To evaluate postoperative subjective quality of vision in patients who underwent Implantable Collamer Lens (ICL) (STAAR Surgical) implantation for correction of myopia and to identify potential predictive parameters. METHODS: In this single-center cross-sectional study, a total of 162 eyes of 81 patients (58 women, 23 men) who underwent ICL implantation were analyzed. The Quality of Vision (QOV) questionnaire was used to assess patient-reported outcomes. Baseline characteristics (eg, age), treatment parameters (eg, surgical corrected refraction), and refractive (eg, residual refraction) and visual (eg, uncorrected distance visual acuity) outcomes were analyzed regarding their effect on QOV. RESULTS: Mean age was 33.3 ± 7.0 years (range: 21 to 51 years) and mean preoperative spherical equivalent was -8.42 ± 2.49 diopters (D) (range: -3.25 to -14.38 D). After a mean postoperative follow-up period of 19 ± 14 months (range: 6 to 54 months), the safety index score was 1.23 ± 0.21 and the efficacy index score was 1.17 ± 0.22. The mean QOV scores were 35.5 ± 11.3, 32.2 ± 11.1, and 23.3 ± 16.1 for frequency, severity, and bothersomeness, respectively. The most frequently experienced symptoms were halos (90.1%) and glare (66.7%). Halos appeared in 66.7% of the patients "occasionally" and 5 of them (6.2%) experienced them "very often." Only 1 patient (1.2%) classified halos as "very bothersome." Patients older than 36 years reported visual symptoms more frequently (P < .05) and showed higher bothersomeness scores (P = .01). CONCLUSIONS: Halos are the most commonly perceived long-term visual disturbance after myopic ICL implantation with a central hole. Visual symptoms can persist more than 6 months postoperatively, causing only minor disturbances in most cases. Older patients seem more prone to experiencing these symptoms. [J Refract Surg. 2022;38(5):280-287.].

Progression of Pachychoroid Neovasculopathy into Aneurysmal Type 1 Choroidal Neovascularization or Polypoidal Choroidal Vasculopathy.

PURPOSE: To describe the progression of pachychoroid neovasculopathy (PNV) into pachychoroid aneurysmal type 1 choroidal neovascularization (PAT1)/polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective longitudinal cohort study. SUBJECTS: Patients diagnosed with PNV with a follow-up of ≥2 years. METHODS: Multimodal imaging, including OCT and fluorescein and indocyanine green angiography, was reviewed for the presence of choroidal neovascularization (CNV), aneurysms within/at the margins of the CNV, and subfoveal choroidal thickness (SFCT). MAIN OUTCOME MEASURES: Rate of PNV to PAT1/PCV conversion and risk factors thereof. RESULTS: In total, 37 eyes of 32 patients with PNV with a mean follow-up of 3.3 ± 1.1 years (range, 2.0-5.2) were included in the study. At PNV diagnosis, the mean age was 59.7 ± 8.7 years (range, 38.5-78.0 years) and mean SFCT was 357 ± 92 µm (185-589). During the follow-up, 5 (13.5%) eyes developed aneurysms after a mean 3.4 ± 0.8 years (2.3-4.2), defining PAT1/PCV. The risk of PAT1/PCV conversion was 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. A mean of 5.2 ± 4.0 to 7.9 ± 3.6 intravitreal anti-VEGF injections were given per year, resulting in a significant reduction of SFCT to 317 ± 104 µm (122-589) (P = 0.0007). The age at diagnosis of PNV was significantly lower in eyes that later went on to develop PAT1/PCV (54.0 ± 5.6 [45.9-60.5] vs. 61.2 ± 8.4 [38.5-78.0] years; P = 0.025). At the end of the follow-up, SFCT had on average decreased by -14.0% ± 17.6% (-55.9% to 23.1%) in the PNV group, whereas it had increased by mean 6.9% ± 4.4% (0.00%-10.8%) in the PAT1/PCV conversion group (P = 0.0025). CONCLUSIONS: PNV can develop aneurysms within its type 1 CNV, defining the conversion to PAT1/PCV. In this study, the conversion to PAT1/PCV was seen in 13.5% of eyes, resulting in Kaplan-Meier estimates of risk for conversion of 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. Younger age at diagnosis of PNV and sustained choroidal thickening despite anti-VEGF therapy might be risk factors for PNV to progress into PAT1/PCV.

Anti-angiogenic properties of rapamycin on human retinal pericytes in an in vitro model of neovascular AMD via inhibition of the mTOR pathway.

PURPOSE: Choroidal neovascularizations (CNV) are partially stabilized through a coverage of pericytes leading to a partial anti-VEGF resistence. Drugs licensed for neovascular AMD (nAMD) do not take this mechanical and growth factor-driven CNV stability into account. The purpose of this work was to see if inhibiting the mammalian target of rapamycin (mTOR) may successfully block angiogenic cellular pathways in primary human retinal pericytes in an in vitro model of nAMD. METHODS: The mTOR inhibitor rapamycin was used to treat human retinal pericytes (HRP) at doses ranging from 0.005 to 15 g/ml. A modified metabolism-based XTT-Assay was used to assess toxicity and anti-proliferative effects. A scratch wound experiment showed the effects on migration. On Cultrex basement membrane gels, the influence of rapamycin on the development of endothelial cell capillary-like structures by human umbilical vein vascular endothelial cells (HUVEC) in the absence and presence of pericytes was investigated. RESULTS: Rapamycin showed no signs of toxicity within its range of solubility. The drug showed dose dependent anti-proliferative activity and inhibited migration into the scratch wound. Endothelial cell tube formation in a HUVEC monoculture was effectively inhibited at 45%. A co-culture of HUVEC with pericytes on Cultrex induced endothelial tube stabilization but was disrupted by the addition of rapamycin leading to degradation of 94% of the tubes. CONCLUSIONS: Rapamycin allows for an efficient modulation of aspects of angiogenesis in pericytes via mTOR-modulation in vitro. Further studies are needed to elucidate whether rapamycin may have an impact on CNV in nAMD in vivo.

Improving morphological outcome in lamellar macular hole surgery by using highly concentrated autologous platelet-rich plasma.

PURPOSE: To evaluate the use of highly concentrated autologous platelet-rich plasma (PRP) in lamellar macular hole (LMH) surgery with regard to function and morphology. METHODS: We included 12 eyes of 12 patients with progressive LMH in this interventional case series. After 23/25-gauge pars plana vitrectomy, 0.1ml highly concentrated autologous platelet-rich plasma was applied under air tamponade. Induction of posterior vitreous detachment and peeling of tractive epiretinal membranes were performed whenever present. Phacovitrectomy was undertaken in cases of phakic lens status. Postoperatively, all patients were instructed to rest in a supine position for the first two postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, spectral-domain optical coherence tomography (SD-OCT), and fundus photography were carried out preoperatively and 6 months postoperatively. RESULTS: Foveal configuration was restored in 10 of 12 patients (83.3%) at 6 months postoperatively. Two patients who had not undergone ILM peeling showed a recurring defect at 6-month follow-up. Best-corrected visual acuity improved significantly from 0.29 ± 0.08 to 0.14 ± 0.13 logMAR (Wilcoxon: p=0.028). Microperimetry remained unchanged (23.38 ± 2.53 preoperatively; 23.0 ± 2.49 dB postoperatively; p=0.67). No patient experienced vision loss after surgery, and no significant intra- or postoperative complications occurred. CONCLUSION: The application of PRP in the surgical therapy of LMH results in good morphological and functional outcomes. Additional peeling of the ILM seems to be mandatory when using PRP to prevent the recurrence of LMH. Strict postoperative supine positioning for 2 h avoids PRP dislocation. Larger sample sizes are needed to confirm the results.