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.

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.

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.

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.

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.

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.

Functional recovery after macula involving retinal detachment and its correlation with preoperative biomarkers in optical coherence tomography.

To introduce an ETDRS grid-based classification for macula involving retinal detachment (MIRD) with or without center (foveal) involvement and to identify biomarkers in preoperative optical coherence tomography (OCT) associated with a favorable postoperative functional outcome in eyes with center involving retinal detachment (CIRD). One hundred and two eyes of 102 consecutive patients (f/m: 35/67) with primary rhegmatogenous retinal detachment, preoperative evidence of MIRD (perifoveal involvement of ≤ 6.0 mm), and successful retinal surgery were included in this retrospective cohort study. Eyes were assigned to 5 grades of MIRD (G1-G5), based on the extent of detachment in the ETDRS grid. Eyes with a detached foveal status (CIRD) were assigned to G4 or G5. In CIRD, the following OCT biomarkers were quantified and correlated with mean BCVA (logMAR) at 3 months postsurgery, using univariate and multivariable regression models: grade of detachment, extent of intraretinal edema, height of foveal detachment, subretinal folds, and epiretinal membrane. Forty-one of 102 eyes (40.2%) presented with an attached foveal status, defined as either outer (G1: 11.8%) or inner (G2: 18.6%) macular involvement or fovea-threatening MIRD (G3: 9.8%). Sixty-one eyes (59.8%) showed CIRD (G4 or G5). Eyes with CIRD had significantly worse postoperative BCVA than eyes without foveal involvement (0.355 logMAR vs. 0.138 logMAR, p<0.001). If CIRD was limited to three outer ETDRS quadrants (G4), mean BCVA was better compared to CIRD involving all four ETDRS quadrants (G5) (0.254 logMAR vs. 0.522 logMAR, p<0.001). Reading ability (BCVA ≤ 0.4 logMAR) was restored in 97.6% of eyes with G1-G3 compared to 86.9% of eyes with G4 (p=0.072) and 52.4% of eyes with G5 (p<0.001). In multivariable regression analysis of eyes with CIRD, a lower grade of detachment (G4 vs. G5: p<0.05) and lower extent of cystoid edema (focal/none vs. wide: p<0.001) were both associated with better postoperative function. The functional outcome after MIRD may be worse in the presence of foveal involvement (CIRD), but a lower grade of detachment and the absence of intraretinal edema can predict a good recovery in spite of CIRD.

Subthreshold laser therapy with a standardized macular treatment pattern in chronic central serous chorioretinopathy.

PURPOSE: There is an ongoing controversial debate about the effectiveness of laser treatments in chronic central serous chorioretinopathy (cCSC). We performed a prospective non-randomized interventional study to learn about the effects of a subthreshold laser treatment (Topcon Endpoint Management™, Topcon Healthcare Inc., Tokyo, Japan) in patients with cCSC. METHODS: Patients with cCSC and a minimum symptom duration of 4 months were included and treated with a standardized laser pattern covering the macular area. Retreatment was performed every 3 months if persistent subretinal fluid was observed. The primary endpoint was resolution of subretinal fluid at 6 months. Further outcome parameters included best corrected visual acuity, microperimetry, central macular and subfoveal choroidal thickness. RESULTS: A total of 42 eyes of 39 patients were included. Mean patient age was 48 ± 10.6 years (range 25-67). Mean symptomatic time before inclusion into the study was 134 ± 133.4 weeks (16-518). Before inclusion, 78.6% of the patients had failed to resolve subretinal fluid under mineralocorticoid receptor antagonists and 14.3% had a recurrence after half-dose photodynamic therapy. Complete resolution of subretinal fluid was observed in 42.9% at 6 months and in 53.8% at 12 months after baseline. Central retinal thickness decreased from 398 ± 135 µm to 291 ± 68 µm (p < 0.001), subfoveal choroidal thickness changed slightly (430 ± 116 µm to 419 ± 113 µm, p = 0.026), microperimetry-derived macular function improved by 19.1 ± 4.7 dB to 21.3 ± 4.8 dB (p = 0.008) and mean BCVA improved by 4.9 ± 8.6 ETDRS letters (p < 0.001). CONCLUSION: The results show that the investigated laser treatment is effective in reducing subretinal fluid and leads to an improvement of functional parameters.

Enlargement rate of geographic atrophy before and after secondary CNV conversion with associated anti-VEGF treatment.

BACKGROUND: To study the enlargement rate of primary geographic atrophy (GA) before and after diagnosis of a secondary choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Five hundred twenty-two consecutive eyes with primary GA were screened for the development of a complicating secondary CNV. Geographic atrophy was measured on blue autofluorescence (BAF) by two readers and calculated into mean growth rate before and after CNV diagnosis. RESULTS: Ten eyes of six patients were included in the study (six study eyes with GA complicated by CNV, four GA only partner eyes). Follow-up was 1.42 ± 0.48 years before and 3.64 ± 2.73 years after CNV. There was no significant difference between mean growth rate before and after CNV (1.58 ± 0.99 vs. 1.39 ± 0.65 mm2/year; p = 0.44) or between study and partner eyes (p = 0.86). Over a mean time of 3.64 ± 2.73 years, a mean of 8.3 ± 2.8 anti-VEGF injections were given. No correlation between the amount of anti-VEGF injections and change in growth rate could be observed (r = 0.58; p = 0.23). CONCLUSION: In this pilot study, primary GA enlargement did not seem to be influenced by a secondary CNV. No association between the intensity of anti-VEGF treatment and changes in atrophy enlargement rates were found. Further studies with larger sample sizes are warranted.

Long-term ocular damage after recovery from COVID-19: lack of evidence at three months.

IMPORTANCE: A small number of COVID-19 patients has been reported to suffer from acute keratoconjunctivitis. In very rare cases, acute inflammatory retinal vein occlusion, papillophlebitis or retinopathy have been observed. OBJECTIVE: To determine possible long-term effects on the eye, especially on the retina, in patients who had suffered from COVID-19 at least 3 months after recovery. DESIGN: Prospective cross-sectional study. SETTING: Hospital of the Ludwig Maximilians University, Munich. PARTICIPANTS: Patients who had been tested positive for SARS-CoV-2 or for anti-SARS-CoV-2 IgG serum antibodies in the Hospital of the Ludwig Maximilians University, Munich between May and September. METHODS: Patients who had tested positive were either hospitalized or discharged into home quarantine via the emergency room. Three months after recovery, they were invited to participate voluntarily for this study during their follow-up in our clinic. A complete ophthalmological exam including functional and imaging end points (including optical coherence tomography (OCT), OCT angiography) was performed. MAIN OUTCOMES AND MEASURES: Visual acuity, slit lamp, bio microscopy and fundoscopy, multimodal imaging findings. RESULTS: In total, 21 patients were examined. The mean age (SD) of the patients was 48.7 (18.3) years. Of these, 14 (66.6%) were hospitalized and 7 (33.3) were discharged home. Two hospitalized patients (9.5%) received invasive ventilation. During the infection, 14 of the 21 patients (66.6%) were in regular care whereas 2 patients (9.5%) received intensive care ventilation for 8.5 (SD) (0.7) days on average in the COVID ICU. Ophthalmological examination of the previously hospitalized group took place 111.4 (23.2) days after recovery and discharge from the hospital, while non-hospitalized patients were examined after mean 123.4 (44.7) days. All patients showed normal findings for anterior and posterior segment of both eyes. OCT and OCT-A showed no evidence of retinal damage, or vascular or microvascular events. CONCLUSION AND RELEVANCE: This study with a small prospective cohort of 21 patients indicates that there might be no evidence of ocular complications at 3 months after recovery from COVID-19, without previous eye involvement. Further studies with more participants with and without acute ocular symptoms are necessary for final evidence.

Vanishing pachy-choroid in pachychoroid neovasculopathy under long-term anti-vascular endothelial growth factor therapy.

BACKGROUND: To investigate the diagnostic value of choroidal thickness in the definition of pachychoroid neovasculopathy (PNV), especially in eyes treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Twenty-two consecutive eyes of 11 patients with uni- or bilateral PNV were analyzed. Anti-VEGF treatment was correlated with changes in choroidal thickness on enhanced depth imaging optical coherence tomography. RESULTS: There were 14 eyes with PNV and 8 non-neovascular partner eyes. Mean age was 64.2 ± 4.0 (range: 60-72), total follow-up was 1.8 ± 0.4 (1-2) years. In PNV eyes, choroidal thickness at baseline was 400 ± 58 (269-485) µm. After two years and 13 anti-VEGF injections on average, a mean reduction of - 39 ± 10 (- 26 to - 56) % to final 241 ± 52 (162-327) µm was observed (p < 0.0001). Meanwhile, choroidal thickness in the partner eyes remained stable (p > 0.13 for all comparisons). A significant correlation of choroidal thinning and anti-VEGF injection rate was observed at year one (r = - 0.79; R2 = 0.63; p = 0.00073) and two (r = - 0.69; R2 = 0.48; p = 0.019). While 85.7% of PNV eyes exceeded a pachychoroid threshold of ≥350 µm at baseline, this figure dropped to 21.4% at year one and 0% at year two. CONCLUSION: In PNV, choroidal thickness significantly decreases with anti-VEGF therapy, resembling a "vanishing pachy-choroid", and thus does not represent a valid long-term diagnostic criterium, especially when differentiating PNV from nAMD.

Minimal Residual Disease in Neovascular Age-Related Macular Degeneration.

With the advent of long-acting anti-vascular endothelial growth factor substances, "healing of AMD (age-related macular degeneration)" might be easily assumed due to prolonged treatment intervals. Adoption of the oncological concept of minimal residual disease for quiescent choroidal neovascularization (CNV) lesions might enhance the importance of continued monitoring, and spur research into the core of the disease, i.e., CNV biology.

Highly Concentrated Autologous Platelet-Rich Plasma Restores Foveal Anatomy in Lamellar Macular Hole Surgery.

BACKGROUND: Lamellar macular holes (LMHs) are an entity of a progressive disease in which the efficacy of the therapy of choice, vitrectomy, seems to be reduced. It is unknown whether highly concentrated autologous platelet-rich plasma (PRP) is of value in the therapy of LMHs. The purpose of this study was to gauge the potential of highly concentrated PRP to restore foveal anatomy in LMH surgery. PATIENTS AND METHODS: In this interventional case series, eight eyes of eight patients with progressive LMH were included. All patients underwent a 23-gauge pars plana vitrectomy with induction of a posterior vitreous detachment and peeling of tractive epiretinal membranes whenever present. Under air tamponade, 0.1 mL of highly concentrated autologous PRP was applied. Subsequently, a gas or air tamponade was performed. All patients were instructed to rest in the supine position for the first 1 to 2 postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, spectral-domain optical coherence tomography (SD-OCT) and fundus photography were performed prior to and 3 months after surgery. RESULTS: SD-OCT showed closure of the macular defect with restoration of a normal foveal configuration in all (8 of 8) patients 3 months postoperatively. BCVA improved significantly, from 0.28 ± 0.08 to 0.12 ± 0.14 logMAR (Wilcoxon: p = 0.03). Microperimetry remained unchanged (24.13 ± 1.96 vs. 23.7 ± 1.54 dB; p = 0.46). No clinically significant intra- or postoperative complications were observed. CONCLUSION: The use of highly concentrated PRP enables excellent anatomical and functional outcomes in the surgical therapy of LMH. Further prospective comparative trials are warranted to compare this promising technique with existing surgical strategies.

Effects of the First COVID-19 Lockdown on Ophthalmological Patient Care.

PURPOSE: To determine the effect of lockdown on medical care, with the example of ophthalmology. METHODS: Patients in a period during the first lockdown were compared to a non-lockdown period, with a total of 12 259 patients included in an observational study. Changes in different areas (elective, emergency, inpatients, surgeries) and eye care subspecialties were compared. Emergency patients were analyzed according to severity and urgency. Patients showing hints requiring treatment for urgent cardiovascular diseases were determined. Differences in patients who would have suffered severe vision loss without treatment were identified and the QALY (quality-adjusted life years) loss was determined accordingly. A model to prioritize patient visits after the end of lockdown or in future lockdown scenarios was developed. Data were collected at the University Eye Hospital LMU Munich and patient files were reviewed individually by ophthalmologists. RESULTS: The average patient number decreased by - 59.4% (p < 0.001), with a significant loss in all areas (elective, emergency, inpatients, surgeries; p < 0.001). There was a decline of - 39.6% for patients at high risk/high severity. Patients with indications of a risk factor of future stroke declined significantly (p = 0.003). QALY loss at the university eye hospital was 171, which was estimated to be 3160 - 24 143 for all of Germany. Working up high losses of outpatients during these 8 weeks of projected lockdown in Germany would take 7 - 23 weeks under normal circumstances, depending on ophthalmologist density. The prioritization model can reduce morbidity by up to 78%. CONCLUSION: There was marked loss of emergency cases and patients with chronic diseases. Making up for the losses in examinations and treatments will theoretically take weeks to months. To reduce the risk of morbidity, we recommend a prioritization model for rescheduling and future lockdown scenarios.

Response of neovascular central serous chorioretinopathy to an extended upload of anti-VEGF agents.

PURPOSE: To determine the anatomical and functional outcomes of an extended 6-month intravitreal anti-vascular endothelial growth factor (anti-VEGF) upload in choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). METHODS: A retrospective database analysis was performed applying the following inclusion criteria: (1) diagnosis of CSCR, (2) diagnosis of secondary CNV, and (3) treatment of at least six consecutive injections of anti-VEGF. Outcome measures included the change of central retinal subfield thickness, remodeling of the pigment epithelium detachments, and change in visual function. RESULTS: Twenty-one eyes of 21 patients were included. Mean patient age was 65 ± 8.3 years, and 35% of the patients (n = 8) were female. Mean disease duration before diagnosis of CNV was 48 ± 25.3 months. Mean central retinal thickness decreased from 346 ± 61 to 257 ± 57 µm (p < 0.01) after the sixth injection while mean visual acuity improved from 0.65 ± 0.35 to 0.49 ± 0.29 (logMAR; p < 0.01). Of note, an extended upload of six as opposed to three injections yielded an additional mean central retinal thickness reduction (280 ± 46 µm vs. 257 ± 57 µm, p = 0.038). Significant CNV remodeling was observed as a decrease in pigment epithelium detachment (PED) vertical (p = 0.021) and horizontal diameter (p = 0.024) as well as PED height (p < 0.01). CONCLUSION: An extended anti-VEGF upload of six consecutive injections seems to be effective in inducing CNV remodeling and fluid resorption in CNV complicating chronic CSCR.

COVID-19: Ophthalmological Aspects of the SARS-CoV 2 Global Pandemic. / COVID-19: ophthalmologische Aspekte der globalen SARS-CoV-2-Pandemie.

PURPOSE: To perform a systematic analysis of articles on the ophthalmological implications of the global COVID-19 pandemic. METHODS: PubMed.gov was searched for relevant articles using the keywords "COVID-19", "coronavirus", and "SARS-CoV-2" in conjunction with "ophthalmology" and "eye". Moreover, official recommendations of ophthalmological societies were systematically reviewed, with a focus on the American Academy of Ophthalmology (AAO) and the Royal College of Ophthalmologists (RCOphth). RESULTS: As of April 16, 2020, in total, 21 peer-reviewed articles on the ophthalmological aspects of COVID-19 were identified. Of these, 12 (57.1%) were from Asia, 6 (28.6%) from the United States of America, and 3 (14.3%) from Europe. There were 5 (23.8%) original studies, 10 (47.6%) letters, 3 (14.2%) case reports, and 3 (14.2%) reviews. These articles could be classified into the topics "Modes and prevention of (ocular) transmission", "Ophthalmological manifestations of COVID-19", "Clinical guidance concerning ophthalmological practice during the COVID-19 pandemic", and "Practical recommendations for clinical infrastructure". Practical recommendations could be extracted from official statements of the AAO and the RCOphth. CONCLUSION: Within a short period, a growing body of articles has started to elucidate the ophthalmological implications of COVID-19. As the eye can represent a route of infection (actively via tears and passively via the nasoacrimal duct), ophthalmological care has to undergo substantial modifications during this pandemic. In the eye, COVID-19 can manifest as keratoconjunctivitis.

Combined VEGF/PDGF inhibition using axitinib induces αSMA expression and a pro-fibrotic phenotype in human pericytes.

PURPOSE: Large trials on anti-VEGF/PDGF (vascular endothelial/platelet-derived growth factor) combination therapy have been established to improve management of neovascular activity in age-related macular degeneration. Targeting pericytes, PDGF is thought to induce vessel regression and reduce fibrovascular scarring. The fate of pericytes exposed to anti-VEGF/PDGF combination therapy is not clear. Therefore, this study was designed to study the influence of anti-VEGF/PDGF on pericyte phenotype and cellular behavior. METHODS: Human pericytes from placenta (hPC-PL) were treated with axitinib, a tyrosine kinase inhibitor targeting VEGFR1-3 and PDGFR. Toxic effects were excluded using live/dead staining. Phenotypic changes were evaluated using phalloidin staining for actin cytoskeleton and the expression of stress fibers. MRNA and protein expression levels of α-smooth muscle actin (αSMA) as a marker of proto-myofibroblastic transition were evaluated with real-time PCR and Western blotting. Influences of fibrotic cellular mechanisms were evaluated with a scratch wound migration and a collagen gel contraction assay. RESULTS: Treatment with 0.5, 1, and 2.5 µg/ml axitinib strongly induced a proto-myofibroblast-like actin cytoskeleton with a marked increase in stress fibers. Quantitative real-time PCR and Western blotting revealed these changes to be linked to dose-dependent increases in αSMA mRNA and protein expression. However, fibrotic cellular mechanisms were significantly reduced in the presence of axitinib (scratch wound closure: up to - 78.4%, collagen gel contraction: up to - 37.4%). CONCLUSIONS: Combined anti-VEGF/PDGF inhibition seems to induce a proto-myofibroblast-like phenotype in human pericytes in vitro, but reduce profibrotic cellular mechanisms due to prolonged anti-PDGF inhibition.

Combined VEGF and PDGF inhibition for neovascular AMD: anti-angiogenic properties of axitinib on human endothelial cells and pericytes in vitro.

PURPOSE: Drugs currently approved for neovascular age-related macular degeneration (nAMD) offer anti-VEGF monotherapy only. Platelet-derived growth factor (PDGF) signaling is pivotal to pericyte-induced stabilization of choroidal neovascularizations (CNV), and causes partial anti-VEGF resistance. No combination therapy for VEGF and PDGF has been approved yet. Axitinib is a tyrosine kinase inhibitor interfering with VEGF and PDGF signaling, and has been approved for the treatment of renal cell carcinoma. This study evaluates anti-angiogenic properties of axitinib in an in-vitro model of choroidal neovascularizations in nAMD. METHODS: Human endothelial cells (HUVEC) and human pericytes (hPC-PL) were treated with axitinib doses ranging from 1.0 ng/ml to 10 µg/ml. Cellular viability and proliferation were assessed with a modified MTT assay. VEGF- and PDGF-stimulated migration was observed in modified Boyden chambers. Formation of capillary structures was evaluated on Cultrex basement membrane. RESULTS: Proliferation was significantly inhibited in both cell lines in a dose-dependent manner. VEGF and PDGF significantly induced, whereas simultaneous axitinib normalized cellular migration in HUVEC and pericytes. On growth-factor-reduced Cultrex, VEGF induced the formation of capillary structures, while axitinib significantly reverted this effect. Axitinib reduced the amount of vessel associated tissue on full growth factor Cultrex. All effects on both cell lines were observed in non-toxic concentrations of axitinib. CONCLUSIONS: Axitinib inhibits angiogenesis in endothelial cells and pericytes via VEGFR and PDGFR modulation in vitro. Further studies are needed to elucidate whether axitinib may also improve therapy of CNV in AMD in vivo by interference with pericyte stabilization of pathological vessels.

EGFR inhibitor Gefitinib attenuates posterior capsule opacification in vitro and in the ex vivo human capsular bag model.

PURPOSE: Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Gefitinib is a selective inhibitor of the epidermal growth factor receptor (EGFR) which represents a potential pharmacological target for PCO prevention. In this in vitro study, we assessed the effect and biocompatibility of Gefitinib in PCO prophylaxis. METHODS: The effect of Gefitinib on the key pathological features of PCO was assessed in vitro. We determined growth in the human capsular bag model, prepared from sixteen cadaver eyes that underwent sham cataract surgery. Furthermore, two lens epithelial cell lines, HLE-B3 and FHL-124, were used to determine concentration-based effects on cell proliferation. In addition, cell-migration, matrix-contraction, and cell spreading were investigated. To exclude toxic concentrations, Gefitinib was assessed for its biocompatibility on six different human ocular cell types from the anterior and posterior segment of the eye. RESULTS: Gefitinib significantly increased the time until confluence of the capsular bag compared to controls (p < 0.001)). In both human lens epithelial cell lines (HLE-B3 and FHL-124), proliferation decreased significantly and as equally strong after incubation with Gefitinib (p < 0.001), as did chemotactic migration (p = 0.004), matrix contraction (p = 0.001), and cell-spreading (p = 0.001). At the IC50 concentration, Gefitinib was well tolerated by six different human ocular cell types of the anterior and posterior segment. CONCLUSION: The specific EGFR inhibitor Gefitinib might become of clinical relevance in PCO prophylaxis as it attenuated cellular growth and other pathological PCO factors in the ex vivo human capsular bag model and in two human lens epithelial cell lines, while showing good biocompatibility in vitro.