LASER FLARE PHOTOMETRY IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: An Evaluation of 2,487 Cases.

PURPOSE: Exploratory analysis associated with the prospective, multicenter, randomized PRIVENT trial. To characterize the associations between laser flare photometry and anatomical and epidemiological features of rhegmatogenous retinal detachment (RRD). METHODS: The authors measured laser flare values of all 3,048 prescreened patients excluding those with comorbidities. A mixed regression analysis evaluated the strength of the influencing factors like age, sex, lens status, and presence and extent of RRD on laser flare. RESULTS: Rhegmatogenous retinal detachment was more frequent in men (65.8%) than in women (34.2%, P < 0.001) and in right (52%) than in left eyes (48%, P = 0.045). Phakic RRD affected less quadrants and was less likely to be associated with macula-off status than pseudophakic RRD (48.4% vs. 58.0% macula off, 23% vs. 31% ≥3 quadrants, P < 0.001). Laser flare of affected eyes was significantly higher compared with fellow eyes (12.6 ± 15.2 vs. 8.3 ± 7.4 pc/ms, P < 0.001). The factors age, sex, lens status, presence of RRD, and the number of quadrants affected were independent influencing factors on laser flare. R 2 was 0.145 for phakic and 0.094 for pseudophakic eyes. CONCLUSION: The results indicate that there may be more factors affecting laser flare than previously assumed. This might limit flare as predictive value for PVR and retinal redetachment.

Optic Nerve Sheath Diameter for Assessing Prognosis after Out-of-Hospital Cardiac Arrest.

PURPOSE: Evaluate optic nerve sheath and pial diameters (ONSD, ONPD) via sonography and computed tomography (CT) after out-of-hospital cardiac arrest (CA) and to compare their prognostic significance with other imaging and laboratory biomarkers. MATERIALS AND METHODS: A prospective observational study enrolling patients after successful resuscitation between December 2017 and August 2021. ONSD and ONPD were measured with sonography. Additionally, ONSD, and also grey-to-white ratio at basal ganglia (GWRBG) and cerebrum (GWRCBR), were assessed using CT. Lactate and neuron specific enolase (NSE) blood levels were measured. RESULTS: Sonographically measured ONSD and ONPD yielded no significant difference between survival and non-survival (p values ≥0.4). Meanwhile, CT assessed ONSD, GWRBG, GWRCBR, and NSE levels significantly differed regarding both, survival (p values ≤0.005) and neurological outcome groups (p values ≤0.04). For survival prognosis, GWRBG, GWRCBR, and NSE levels appeared as excellent predictors; in predicting a good neurological outcome, NSE had the highest accuracy. CONCLUSIONS: CT diagnostics, in particular GWRBG and GWRCBR, as well as NSE as laboratory biomarker, appear as excellent outcome predictors. Meanwhile, our data lead us to recommend caution in utilizing sonography assessed ONSD and ONPD for prognostic decision-making post-CA.

Evaluation of a Novel Non-Diffractive Extended Depth of Focus Intraocular Lens - First Results from a Prospective Study.

PURPOSE: To evaluate a novel hydrophobic, non-diffractive, extended depth of focus (EDOF) intraocular lens (IOL) design in comparison to two monofocal aspheric lenses. METHODS: Inclusion criteria for this prospective, monocentric cohort study were opacification of the crystalline lens and patients' wishes for surgery. In the case of the EDOF IOL, patients asked for a presbyopia correction. All patients received surgery on both eyes. Corrected and uncorrected distance visual acuity (CDVA, UCDVA), uncorrected and distance corrected intermediate visual acuity (UIVA, DCIVA) and defocus curves (all monocular and binocular) were compared three months postoperatively. RESULTS: Fifty-six eyes were implanted with an EDOF IOL (LuxSmartTM, Bausch & Lomb GmbH, Berlin, Germany), 50 eyes with a monofocal aspheric IOL: 32 eyes with a clear IOL (Polylens® AS 61, Polytech Domilens, Roßdorf, Germany), 16 eyes with a yellow IOL (iSert® 251, Hoya Surgical Optics GmbH, Frankfurt, Germany). Three months postoperatively, UCDVA was comparable with the EDOF IOL, versus the monofocal IOL (P > 0.9). Binocular DCIVA in the EDOF IOL was significantly higher than in the monofocal IOL (P = 0.001). Monocular DCIVA better than 20/23 Snellen was achieved in 10% with the monofocal IOL and in 68% (P < 0.0001) with the EDOF IOL. Defocus curves showed a depth of focus at 20/23 Snellen of 1.6 vs. 0.83 diopters (D) in the EDOF IOL, vs. the monofocal IOL. No patient reported halos or starbursts in non-standardized questioning. CONCLUSION: This non-diffractive EDOF IOL provided comparably high UCDVA and significantly higher DCIVA than the mono-focal lenses, causing only mild optical phenomena.

Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial.

PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

[Application of rebound self-tonometry for measurements in a supine position]. / Einsatzmöglichkeit von Rebound-Selbsttonometrie zur Liegendmessung.

BACKGROUND: Diurnal or nocturnal fluctuations of intraocular pressure (IOP), which are especially common in glaucoma patients, often require hospitalization of the patient in order to be detected. This is often inconvenient for the patient. Therefore, this study evaluated the usefulness of a rebound tonometer (RT) designed for IOP self-tonometry (RT-Home) in an outpatient department, especially in the supine position and out of office hours. METHODS: Over a period of 6 months unselected open-angle glaucoma patients were equipped with a RT-home device for one night each. At the beginning IOP values measured by medical personnel (RT-Home(o)) were compared with IOP measured by the patient (RT-Home(p)), as well as measured by applanation tonometry according to Goldmann (GAT). Patients also completed a questionnaire regarding subjective comfort during use of the RT-Home. RESULTS: The RT-Home(o) showed a bias of -1.1 mm Hg (-7.9 to 5.7 mm Hg) compared to GAT and RT-Home(p) showed a bias of -1.6 mm Hg (-8.9 to 5.9 mm Hg) compared to GAT. The measurement differences between GAT and RT-Home(o) as well as RT-Home(p) showed a stong correlation with the IOP and the central corneal thickness (IOP: r = 0.481, P > 0.0001, RT-Home(o) vs. GAT; corneal thickness: r = 0.612, P < 0.0001, RT-Home(o) vs. GAT). The RT-Home(p) in a supine position showed significantly elevated IOP levels than during the day (P < 0.0001). The RT-Home showed no qualitative differences between measurements in supine and sitting positions. DISCUSSION: The RT-Home is effective and precise for use in an outpatient department to gain a general overview over patients' IOP out of office hours and also in the supine position. In the long term it seems possible that RT-Home can avoid hospitalization for diurnal and nocturnal IOP evaluation especially of young, mobile patients; however, interpretation of the data always requires professional knowledge.

Prophylactic intravitreal 5-fluorouracil and heparin to prevent proliferative vitreoretinopathy in high-risk patients with retinal detachment: study protocol for a randomized controlled trial.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is the major cause for postoperative failure after vitreo-retinal surgery for primary rhegmatogenous retinal detachment (RRD). Adjunct pharmaceutical therapy was found to be ineffective once PVR is established. Preliminary data suggest that prevention of PVR yields better functional outcome. So far, there is no standard therapy to prevent PVR. METHODS/DESIGN: This is a randomized, double-blind, controlled, multicenter, interventional trial with one interim analysis. High-risk patients for PVR with primary RRD will be allocated equally to the following treatment arms: (a) verum: intraoperative adjuvant application of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH) via intraocular infusion during routine pars plana vitrectomy (PPV) and (b) placebo: routinely used intraocular infusion with balanced salt solution during routine PPV. PVR risk is assessed by non-invasive aqueous flare measurement by using laser flare photometry. The primary endpoint of the trial is the occurrence of PVR grade CP (C: full-thickness retinal folds or subretinal strands in clock hours; P: located posterior to equator) 1 or higher within 12 weeks after treatment. Secondary endpoints include PVR grade CA (A: located anterior to equator), best corrected visual acuity, number and extent of surgical procedures to achieve retinal re-attachment, and occurrence of drug-related adverse events within 12 weeks. It is assumed, on the basis of previously published results, that the incidence of PVR grade CP 1 is 35% in the control group and that a reduction by one third would be clinically relevant. Given the sequential design and adjustment for a dropout rate of 5%, a total sample size of 560 patients (280 per group) was calculated to ensure a power of 80% for the confirmatory analysis. DISCUSSION: The present trial uses intraoperative intravitreal 5-FU and LMWH as a prophylactic therapy in high-risk patients with primary RRD, aiming to reduce the incidence of PVR in the group that receives the trial drug. Using laser flare photometry to identify high-risk patients for PVR, this trial will test the effectiveness of a simple treatment to prevent PVR. TRIAL REGISTRATION: EudraCT no.: 2015-004731-12, registered October 21, 2015; ClinicalTrials.gov Identifier: NCT02834559 , registered July 12, 2016. Protocol version: Version 02. Date: September 18, 2016.

The influence of systemic renin-angiotensin-inhibition on ocular cytokines related to proliferative vitreoretinopathy.

PURPOSE: The renin-angiotensin system is involved in the pathogenesis of fibrosis in several organs via induction of transforming growth factor (TGF) beta. In the pathogenesis of proliferative vitreoretinopathy (PVR) TGF-beta plays a pivotal role, promoting transition of retinal pigment epithelial (RPE) cells into myofibroblasts. We studied the influence of angiotensin converting enzyme-inhibition (ACEI) on cytokines and growth factors, related to PVR in aqueous humor. METHODS: We performed a post hoc analysis of a prospectively conducted interventional case series. From patients with rhegmatogenous retinal detachment (RRD) aqueous humor was obtained during primary surgery and analyzed using multiplex bead analysis for interferon gamma, tumor necrosis factor alpha, CC-chemokine ligand (CCL) 2 / monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, platelet derived growth factor (PDGF)-aa, TGF-beta 1, TGF-beta 2, TGF-beta 3, fibroblast growth factor (FGF)-aa, and FGF-bb. We recorded information about systemic ACEI from the medical history. RESULTS: In the primary study elevated levels of TGF-beta 1 and 2, IL 6 and 8 and CCL2/MCP-1 were a risk factor for later PVR development. Here, systemic ACEI neither influenced levels of these cytokines and growth factors, nor of any other tested in this study (p ≥ 0.438, respectively). Also the incidence of PVR development was unaffected (p = 0.201). CONCLUSION: The systemic intake of ACEI for arterial hypertension does not influence levels of profibrotic cytokines/growth factors in aqueous humor. Further studies need to clarify if relevant levels of ACEI accumulate in the eye, and if direct administration of ACEI in experimental PVR could be beneficial.

Intensified Early Postoperative Topical Steroids Do Not Influence Endothelial Cell Density After Descemet Membrane Endothelial Keratoplasty Combined With Cataract Surgery (Triple-DMEK).

PURPOSE: To investigate the effect of intensified postoperative topical steroid therapy after Descemet membrane endothelial keratoplasty combined with cataract surgery (Triple-DMEK) on postoperative endothelial cell density (ECD). METHODS: This comparative clinical study with historical controls was conducted at a tertiary hospital, specialized in corneal surgery. Patients undergoing DMEK or Triple-DMEK are included prospectively in the Cologne DMEK Database. Until April 2014, first week's postoperative standard therapy for lamellar keratoplasties was prednisolone acetate eye drops 1% applied 5× daily. After April 2014, first week's postoperative standard therapy changed to prednisolone acetate eye drops 1% applied hourly. We compared 75 consecutive eyes before (group 1) with 75 consecutive eyes after the change of therapy regimen (group 2). Patients received ECD analysis 3 and 6 months after surgery. RESULTS: ECD of grafts in group 1 before transplantation, and 3 months and 6 months after surgery was 2697 ± 218, 1765 ± 349, and 1703 ± 432 cells/mm, respectively. ECD of grafts in group 2 was 2696 ± 267, 1737 ± 450, and 1694 ± 482 cells/mm, respectively. Over 3 and 6 months, ECD in group 1 decreased by 35% ± 13% and 38% ± 18%, respectively. In group 2, ECD decreased by 36% ± 16% and 38% ± 16%, respectively. Neither absolute numbers nor decrease in ECD differed significantly between groups 1 and 2 at any time point (all P > 0.60). CONCLUSIONS: Intensified early postoperative topical steroid therapy during the first postoperative week does not stabilize ECD, nor does it have a toxic effect on endothelial cells during a follow-up of 6 months.

Intensified Topical Steroids as Prophylaxis for Macular Edema After Posterior Lamellar Keratoplasty Combined With Cataract Surgery.

PURPOSE: To analyze the effect of intensified topical steroid therapy after Descemet membrane endothelial keratoplasty combined with cataract surgery (triple-DMEK) on the incidence of postoperative cystoid macular edema (CME). DESIGN: Single-center comparative clinical study with historical controls. SETTING: Department of Ophthalmology, University of Cologne, Germany, tertiary hospital, performing 500 corneal transplant surgeries per year. PATIENTS: Total of 131 patients (150 eyes) undergoing triple-DMEK surgery. Inclusion Criterion: Triple-DMEK surgery. EXCLUSION CRITERIA: Prior retinal surgery, history of prior CME. INTERVENTIONS: Prednisolone acetate eye drops 1% 5 times daily for the first week after surgery. After an internal change of therapy regimen: Prednisolone acetate eye drops 1% hourly for the first postoperative week. We compared 75 consecutive eyes before with 75 consecutive eyes after the change of therapy regimen. Patients received macular spectral-domain optical coherence tomography (SD OCT) preoperatively, as well as 6 weeks and 3 and 6 months post surgery. MAIN OUTCOME MEASURE: Development of CME detected by macular SD OCT during 6 months postoperatively. RESULTS: Both groups were comparable regarding baseline age, sex, central corneal thickness, rebubbling rate, and visual acuity. With topical steroid therapy 5 times per day during the first postoperative week, we observed 9 cases of subsequent CME (12%). With hourly topical steroid therapy none of the patients developed CME subsequently (P = .003). Apart from the topical steroids during the first week, medical treatment was identical in both groups. CONCLUSIONS: Early intensified postoperative topical steroid therapy constitutes an effective prophylactic treatment to reduce incidence of CME after triple-DMEK surgery.

Epithelial-Mesenchymal Transition (EMT)-Related Cytokines in the Aqueous Humor of Phakic and Pseudophakic Fuchs' Dystrophy Eyes.

PURPOSE: The present study aimed to analyze the expression of epithelial-mesenchymal transition (EMT)-related cytokines in the aqueous humor of phakic and pseudophakic Fuchs' endothelial corneal dystrophy (FECD) eyes and their correlation to FECD severity. METHODS: Aqueous humor samples from phakic FECD eyes (FECDph, n = 9), from pseudophakic FECD eyes more than 1 year after cataract surgery (FECDpsph, n = 13), and from cataract controls without FECD (Controlcat, n = 28) were obtained during Descemet membrane endothelial keratoplasty (DMEK) or cataract surgery. Expression of EMT-related cytokines (TGF-ß1, TGF-ß2, TGF-ß3, MCP-1, BFGF, TNF-α, IL-1ß) was measured using multiplex bead assay. Corneal central-to-peripheral thickness ratio at 3.5 mm from the center (CPTR3.5) was determined as an objective metric for FECD severity before surgery by slit-scanning pachymetry. RESULTS: Pseudophakic FECD eyes showed significantly elevated expression compared with Controlcat and FECDph eyes for TGF-ß1 (P < 0.001, respectively), for TGF-ß2 (P < 0.05, respectively), and MCP-1 (P < 0.001, respectively). Levels of TGF-ß1 (r = 0.6116, P < 0.05) and MCP-1 (r = 0.5934, P < 0.05) were positively correlated with CPTR3.5. No differences in EMT-associated protein levels were detected comparing FECDph eyes and Controlcat eyes. CONCLUSIONS: Simultaneous elevation of TGF-ß1, TGF-ß2, and MCP-1 concentrations in FECDpsph eyes confirms that cataract surgery leads to long-term alterations of the intraocular microenvironment. Positive correlation of increased aqueous TGF-ß1 and MCP-1 levels with CPTR3.5 in pseudophakic FECD eyes suggests that changed cytokine levels may be involved in corneal decompensation after cataract surgery. Unchanged aqueous humor levels of EMT-related proteins analyzed in phakic FECD patients indicate that there is no primary role of these aqueous cytokines in FECD pathogenesis.

Fibrovascular pigment epithelial detachment is a risk factor for long-term visual decay in neovascular age-related macular degeneretion.

BACKGROUND: The individual outcome of anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration is variable. To investigate the prognostic value of spectral domain optical coherence tomography structures for best-corrected visual acuity (BCVA) outcome, volumetric analysis of spectral domain optical coherence tomography structures was performed in neovascular age-related macular degeneration correlated with BCVA after 24 months. METHODS: At the Department of Ophthalmology, University of Cologne, Germany, 75 patients with neovascular age-related macular degeneration were analyzed prospectively over 24 months. Patients received three initial consecutive monthly intravitreal ranibizumab injections followed by monthly spectral domain optical coherence tomography controls. Therapy was continued as a pro re nata regimen. Volumetric analysis of spectral domain optical coherence tomography images was performed using commercially available software (3D-Doctor). RESULTS: Subretinal tissue, subretinal fluid, serous pigment epithelial detachment, and fibrovascular pigment epithelial detachment (FPED) were identified. By contrast to all other structures, FPED did not respond to ranibizumab therapy. Volume of FPED at baseline and after the loading phase correlated most with impaired BCVA after 24 months (r = -0.0215, P = 0.9263 [subretinal tissue]; r = -0.3120, P = 0.0216 [subretinal fluid]; r = -0.0757, P = 0.6470 [serous pigment epithelial detachment]; r = -0.4182, P = 0.0111 (FPED baseline); r = -0.4768; P = 0.0002 [FPED after loading phase]). CONCLUSION: Of all identified structures, FPED was most deleterious for BCVA after 24 months. The knowledge about possible BCVA course can influence the decision for more intense treatment regimens.

Upregulation of TGF-ß1 in experimental proliferative vitreoretinopathy is accompanied by epithelial to mesenchymal transition.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is characterized by epithelial to mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells and consecutive formation of fibrous membranes, leading to retinal redetachment. Transforming growth factor beta (TGF-ß) has been suggested to play an important role in this process, but the role of TGF-ß isoforms is unknown. METHODS: In pigmented rabbits (n = 14), PVR was induced by cryopexy and a full-thickness limbus-parallel incision. PVR was evaluated by indirect ophthalmoscopy. Concentrations of TGF-ß isoforms were determined by multiplex bead assay analysis in aqueous humor (AH) and vitreous samples. EMT marker vimentin was analyzed by western blot. Masson's-trichrome, haematoxilin and eosine (H&E), and immunohistochemical analysis for EMT marker alpha SMA were performed on cross-sections of eyes. RESULTS: PVR was induced in all treated eyes. The number of quadrants affected by PVR was 1 (n = 5), 2 (n = 2), 3 (n = 2), 4 (n = 5). Vimentin and alpha SMA were expressed during PVR development. During PVR development, both TGF-ß1 levels (AH: p = 0.001; vitreous: p = 0.002) and TGF-ß2 levels increased (AH: p = 0.027; vitreous: p = 0.02), while TGF-ß3 was not detected at any timepoint. The increase was more pronounced for TGF-ß1 than for TGF- ß2 (AH: p = 0.002; vitreous: p = 0.0005), and only TGF-ß1 correlated with the amount of PVR (p = 0.024, r = 0,723). CONCLUSIONS: Development of PVR membranes was accompanied by a pronounced upregulation of TGF-ß1, rather than TGF-ß2. Therefore TGF-ß1 could be a promising target for inhibition of PVR.

Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment.

BACKGROUND: Aqueous flare as determined by laser flare photometry in the anterior chamber is a strong preoperative predictor for proliferative vitreoretinopathy (PVR) in patients with primary retinal detachment (RD). We analysed various cytokines in aqueous humour samples in relation to aqueous flare and postoperative PVR incidence in patients with RD. METHODS: Preoperatively, the aqueous flare of patients with RD was measured quantitatively with a laser flare metre and aqueous humour samples were collected and analysed for interferon γ, tumour necrosis factor α, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, platelet derived growth factor (PDGF)-aa, transforming growth factor (TGF)-ß1, TGF-ß2, TGF-ß3, fibroblast growth factor (FGF)-aa and FGF-bb by multiplex fluorescent bead-based immunoassays. Three months after RD surgery patients were examined for PVR development. RESULTS: Of 67 consecutive patients, 10 developed at least PVR grade C. Patients with flare values >15 pc/ms (n=20) and the 10 patients with postoperative PVR all had significantly elevated levels of IL-6, IL-8, MCP-1 and TGF-ß1 in aqueous humour (p≤0.05). Levels of VEGF-A, PDGF-aa and TGF-ß2 were not significantly changed. Other cytokines were below the detection threshold. Eight of the 10 patients (80%) with PVR had elevated flare values of >15 pc/ms and 8 of the 20 patients (40%) with flare >15 pc/ms developed PVR. The OR for PVR with flare values >15 pc/ms was 30.7 (p=0.0001). CONCLUSIONS: Laser flare photometry allows simple risk estimation for later PVR development. Elevated laser flare values correspond to an altered profibrotic intraocular cytokine milieu. These factors therefore constitute promising targets for a prophylactic intervention.

Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration.

BACKGROUND: Intravitreal injections of ranibizumab are the standard of care for neovascular age-related macular degeneration (AMD). In clinical trials, comparable efficacy has been shown for either monthly injections or as needed injections upon monthly controls. Unlike in trial settings, treatment in clinical routine is often delayed by complex approval procedures of health insurance and limited short-term surgical capacities. METHODS: Eighty-nine patients with neovascular AMD were followed for 12 months. Early treatment diabetic retinopathy study (ETDRS) visual acuity (VA), Radner reading VA and spectral domain optical coherence tomography were performed monthly, with additional fluorescein angiography if needed. After an initial loading phase of three consecutive monthly intravitreal injections with ranibizumab, re-injections were performed when recurrent activity of choroidal neovascularization (CNV) was detected. RESULTS: After an initial increase to a value of +5.0 ± 11.87 ETDRS letters from baseline, VA constantly decreased over 12 months to a value of -0.66 ± 16.82 ETDRS letters below baseline. Central retinal thickness (CRT) decreased from a value of 438.1 ± 191.4 µm at baseline to a value of 289.9 ± 138.6 µm after initial therapy and stabilized at a value of 322.4 ± 199.5 µm. Loss of VA during latency between indication to treat and treatment was significantly greater than re-gain of VA after re-initiation of therapy (-2.2 ± 5.0 versus 0.4 ± 7.4 letters; p = 0.046). CONCLUSIONS: Latency between indication to treat and treatment is responsible for irreversible VA deterioration. A successful PRN treatment regimen for neovascular AMD requires immediate access to therapy after indication.

In-vivo and ex-vivo characterization of laser-induced choroidal neovascularization variability in mice.

BACKGROUND: Retinal argon laser coagulation is an established procedure for induction of choroidal neovascularization (CNV) in rodents. This study aimed to evaluate the in-vivo and ex-vivo morphology and variability of laser-induced CNV spots over time. METHODS: Female C57/Bl/6 mice, 3-6 months of age, were treated with five spots of retinal argon laser coagulation per eye (150 mW, 100 ms, 50 µm). In-vivo fluorescein angiography (FA) and standard high-resolution spectral-domain optical coherence tomography (SD-OCT) were performed on day (d) 0, d1, d4, d7, d14 and d21. Ex-vivo histology, CD31 immunostaining, flatmount and confocal microscopy were also conducted. CNV size in the retinal and choroidal focus, CNV morphology, central retinal thickness (CRT) and FA CNV activity grading were assessed in-vivo at all times and compared to the ex-vivo assessments. RESULTS: SD-OCT revealed sub-retinal and intra-retinal fluid, and permitted evaluation of longitudinal morphologic changes of the induced CNV. Laser spot area in FA and CRT in SD-OCT did not differ in longitudinal evaluation. CNV could not be consistently outlined on SD-OCT images, and CNV volume as assessed on SD-OCT did not change over time. Significant CNV activity changes were only found in FA CNV activity grading, peaking on d4 and decreasing by d7. CONCLUSIONS: Non-invasive SD-OCT provides additional morphological information on laser-induced CNV. However, reliable evaluation of CNV requires FA. Spontaneous regression of CNV activity within 14 days after induction has to be taken into account when utilizing this model for testing the efficacies of potential future treatments.