[Photo-based examination for diabetic eye pathologies in a German ophthalmological practice without personal doctor-patient contact]. / Fotobasierte Untersuchung auf diabetische Augenveränderungen in einer deutschen Augenarztpraxis ohne direkten Arzt-Patienten-Kontakt.

BACKGROUND: An increasing number of patients suffering from diabetes require regular ophthalmological check-ups to diagnose and/or treat potential diabetic retinal disease. Some countries have already implemented systematic fundus assessments including artificial intelligence-based programs in order to detect sight-threatening retinopathy. The aim of this study was to improve the detection of diabetic fundus changes in Germany without examination by a doctor and to create an easy access to ophthalmological examinations. MATERIAL AND METHODS: In this prospective monocentric study 93 patients in need for a routine check-up for diabetic retinopathy were included. The study participants took up an offer of an examination (visual examination, non-mydriatic camera-based fundus examination) without doctor-patient contact. Patient satisfaction with the organization and examinations was assessed using a questionnaire. RESULTS: The mean age was 53.5 years (SD 13.6 years, 49.5% female) and 17 eyes (18.3%) showed a diabetic retinopathy which was detected using a camera-based examination. Within the small sample, no patient had to repeat the examination due to poor image quality. All categories of the questionnaire showed a good to very good satisfaction, indicating a high acceptance of the other examination form that took place at the ophthalmologist's premises. CONCLUSION: In our study in an ophthalmological practice a high level of acceptance among the patients interested in the screening for diabetic retinopathy without any direct patient-doctor contact was achieved. Our study shows a very good acceptance and feasibility. Future use of artificial intelligence in clinical practice may help to be able to screen many more patients as in this study imaging quality was very good.

Detection of SARS-CoV-2-RNA in post-mortem samples of human eyes.

PURPOSE: To detect SARS-CoV-2 RNA in post-mortem human eyes. Ocular symptoms are common in patients with COVID-19. In some cases, they can occur before the onset of respiratory and other symptoms. Accordingly, SARS-CoV-2 RNA has been detected in conjunctival samples and tear film of patients suffering from COVID-19. However, the detection and clinical relevance of intravitreal SARS-CoV-2 RNA still remain unclear due to so far contradictory reports in the literature. METHODS: In our study 20 patients with confirmed diagnosis of COVID-19 were evaluated post-mortem to assess the conjunctival and intraocular presence of SARS-CoV-2 RNA using sterile pulmonary and conjunctival swabs as well as intravitreal biopsies (IVB) via needle puncture. SARS-CoV-2 PCR and whole genome sequencing from the samples of the deceased patients were performed. Medical history and comorbidities of all subjects were recorded and analyzed for correlations with viral data. RESULTS: SARS-CoV-2 RNA was detected in 10 conjunctival (50%) and 6 vitreal (30%) samples. SARS-CoV-2 whole genome sequencing showed the distribution of cases largely reflecting the frequency of circulating lineages in the Munich area at the time of examination with no preponderance of specific variants. Especially there was no association between the presence of SARS-CoV-2 RNA in IVBs and infection with the variant of concern (VOC) alpha. Viral load in bronchial samples correlated positively with load in conjunctiva but not the vitreous. CONCLUSION: SARS-CoV-2 RNA can be detected post mortem in conjunctival tissues and IVBs. This is relevant to the planning of ophthalmologic surgical procedures in COVID-19 patients, such as pars plana vitrectomy or corneal transplantation. Furthermore, not only during surgery but also in an outpatient setting it is important to emphasize the need for personal protection in order to avoid infection and spreading of SARS-CoV-2. Prospective studies are needed, especially to determine the clinical relevance of conjunctival and intravitreal SARS-CoV-2 detection concerning intraocular affection in active COVID-19 state and in post-COVID syndrome.

[The Eye in Internal Medicine: Diabetic retinopathy]. / Das Auge in der Inneren Medizin: Die diabetische Retinopathie.

Diabetic retinopathy has seen tremendous progress in diagnostic tools and treatment in recent 15 years. Sight threatening stages like proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) can be treated much more effectively now. The recognition of vascular endothelial growth factor (VEGF) as a driver of proliferation and macular edema has led to the development of VEGF inhibiting drugs such as antibodies (Bevacizumab), fragments of an antibody (Ranibizumab), or a so called VEGF trap (Aflibercept). Laser treatment is no longer a gold standard. Today laser therapy is part of a combined treatment strategy. DME can be monitored quantitatively by ocular coherence tomography (OCT) measurements. For non-responders to VEGF inhibiting drugs, we have secondline corticosteroidal implants. However, screening examinations and early diagnosis of DME and PDR remain crucial. The same accounts for the collaboration of opthalmologists, general practioners, and diabetologists. Good control of diabetes and blood pressure is still important.

[Cost Comparison of Licensed Intravitreal Therapies for Insufficiently Anti-VEGF Responding Fovea Involving Diabetic Macular Edema in Germany]. / Kostenvergleich zugelassener intravitrealer Therapien bei nicht ausreichend auf primäre Therapie ansprechendem diabetischem Makulaödem mit fovealer Beteiligung in Deutschland.

BACKGROUND: In the treatment of center-involving diabetic macular edema, despite initial therapy with an anti-VEGF compound, an insufficient response may occur. Further therapy options include a switch of anti-VEGF products or to corticosteroid implants, such as Fluocinolone acetonide or Dexamethasone. OBJECTIVES: Firstly, to investigate systematically which evidence-based study data are available describing the efficacy of in-label treatments after primary anti-VEGF treatment, secondly, to investigate which costs go along for the healthcare provider. METHODS: A systematic literature review (SLR) for randomized controlled trials (RCT) was performed in Medline and Embase. A short-term cost-cost model was built in MS Excel with a 3 year time horizon to compare in-label intravitreal options Ranibizumab (Lucentis®), Aflibercept (Eylea®), Fluocinolone acetonide implant (Iluvien®), and Dexamethasone implant (Ozurdex®). Cost components comprised of drug and injection costs, optical coherence tomography (OCT) procedures, and adverse events such as endophthalmitis, IOP-lowering drugs and surgery and cataract surgery. RESULTS: A total of 42 publications of 20 RCTs were identified. No study had a clearly defined population after first line anti-VEGF treatment, thus no direct efficacy comparison was possible. In the short-term cost-cost model total costs were 17,542 € for Ranibizumab, 15,896 € for Aflibercept, 10,826 € for Fluocinolone acetonide implant and 12,365 € for Dexamethasone implant. For all treatment regimens, drug costs were the predominant cost component, followed by injection costs (with variations dependent on the specific drug) and OCT costs. In the uni- and multivariate sensitivity analyses, the results obtained were robust to changes of model inputs. CONCLUSIONS: In summary, the short-term cost-cost comparison demonstrates that steroid implants can provide significant cost savings versus in-label anti-VEGF treatment for center-involving diabetic macular edema. Single application of the long-lasting Fluocinolone acetonide implant is the most cost-efficient in-label treatment option.

Evaluation of a computed-tomography-based assessment scheme in treatment decision-making for isolated orbital floor fractures.

INTRODUCTION: Treatment decisions for fractures of the orbital floor are based on clinical appearance, ophthalmological examination, and computed tomography (CT) scans. In extensive fractures, decisions are easily made between conservative and surgical treatment. However, objective parameters are rare in inconclusive cases. MATERIALS AND METHODS: Our retrospective study included 106 patients with unilateral isolated orbital floor fractures. Correlations between preoperative ophthalmological examinations and specific CT parameters were performed. RESULTS: The defect size of the fracture appeared to be significantly associated with the presence of diplopia. CT-morphological parameters and preoperative ophthalmological results showed statistical significance for diplopia and incarceration of inferior rectus muscle (IRM), diplopia and displacement of IRM, decreased mobility and incarceration of IRM, and decreased mobility and displacement of IRM. DISCUSSION: Our clinical assessment scheme for CT scans of orbital floor fractures is aimed at facilitating treatment decision making using four CT-based variables. As critical size defects of the orbital floor of ≥2 cm2 are likely to cause clinically significant posterior displacement of the globe, resulting in enophthalmos, the proposed parameters offer a readily accessible and easy to evaluate scheme that helps to identify patients in need of surgical intervention.

A noninterventional study to monitor patients with diabetic macular oedema starting treatment with ranibizumab (POLARIS).

PURPOSE: Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real-world settings. METHODS: POLARIS was a noninterventional, multicentre study to monitor 12-month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency. RESULTS: Outcomes were analysed from all treated patients (n = 804) and from first-year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3-5.4) at month 12 (study eye; first-year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first-year completers). The mean (SD) baseline CRT was 410.6 (128.8) µm, and the mean change in CRT was -115.2 µm at month 12 (study eye; first-year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters). CONCLUSION: POLARIS showed that real-world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring.

Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema.

OBJECTIVE: To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections required for treatment of diabetic macular edema (DME). RESEARCH DESIGN AND METHODS: A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12. RESULTS: Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p = 0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88 ± 1.23 vs. 3.88 ± 2.32, p< = 0.001). By month 12, 84% of patients in the monotherapy group had required additional ranibizumab injections as compared to 35% in the combination group (p< = 0.001). CONCLUSIONS: Navigated laser combination therapy demonstrated significant visual gains in most patients. Retreatment rate and number of injections were significantly lower compared to ranibizumab monotherapy and compared to the results of conventional laser combination therapy previously reported in pivotal anti-VEGF studies.

Visual acuity and central retinal thickness: fulfilment of retreatment criteria for recurrent neovascular AMD in routine clinical care.

BACKGROUND: To evaluate the fulfillment of retreatment criteria in recurrent neovascular age-related macular degeneration (nAMD) for a pro-re-nata treatment regime with ranibizumab in routine clinical care. METHODS: Data from patients with treatment-naive nAMD were analysed retrospectively. As an 'upload', all patients had received three-monthly intravitreal ranibizumab injections in a university eye hospital and were then seen by ophthalmologists in private practice who referred them back in case of recurrence. Recurrence was defined as a decrease of visual acuity (VA) of one line or more (functional retreatment criteria), a central retinal thickness (CRT) increase of at least 100 µm upon Optical Coherence Tomography (OCT) examination (morphological retreatment criteria) or a new macular haemorrhage (clinical retreatment criteria). RESULTS: We included 92 patients (36 men and 56 women). The mean VA before retreatment of a recurrence was -0.63 ± 0.33 logMAR and improved significantly (p<0.001) by 0.10 ± 0.16 logMAR to -0.53 ± 0.28 logMAR thereafter. Mean CRT before retreatment was 278.07 ± 87.56 µm and decreased significantly (p<0.001) by 71.22 ± 106.93 to 206.85 ± 60.30 µm. Evaluation of the fulfillment of retreatment criteria revealed functional retreatment criteria in 82.6% of patients. However, upon re-evaluation of VA using Early Treatment Diabetic Retinopathy Study (ETDRS) charts in the treatment centre, mean decrease of VA was 10 letters as compared with the end of upload therapy. All patients presented an increased CRT when treated for recurrence of nAMD (mean increase 69.47 µm), but the morphological retreatment criteria (CRT increase of 100 µm or more) were fulfilled in only 44.4% of patients upon Spectral Domain OCT (SD-OCT) evaluation in the treatment centre. CONCLUSIONS: In a routine clinical care, evaluation of VA using ETDRS charts seems to be more sensitive than Snellen VA testing. Quantitative OCT-based retreatment criteria (eg, increase of CRT of 100 µm or more) appear to be not sensitive enough in a clinical setting with referring ophthalmologists.

Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR image analysis--potential role as biomarker of response to ranibizumab treatment.

PURPOSE: To evaluate the influence of a ranibizumab treatment on microaneurysm (MA) turnover in diabetic retinopathy. METHODS: Sixty-nine eyes were included in this retrospective study. We compared a group of 33 eyes with ranibizumab treatment for diabetic macular edema to 36 eyes with nonproliferative diabetic retinopathy only. Nonmydriatic ultra-widefield scanning laser ophthalmoscopy (Optomap) images were obtained at a mean 4.76 ± 1.69 days prior to the first ranibizumab injection (baseline) and again 35.94 ± 2.44 days after the third consecutive injection in a 4-week interval. In untreated controls, images were obtained at baseline and 97.81 ± 3.16 days thereafter. Images were analyzed using the RetmarkerDR software (Critical Health SA, Coimbra, Portugal), and the turnover of MAs was documented and analyzed. Thereafter, MA turnover was correlated with central retinal thickness (CRT) as assessed by OCT. RESULTS: At baseline, patients in the treatment group had 5.64 ± 0.75 MAs. One month after 3 ranibizumab injections, measured MAs decreased to 4.03 ± 0.66. In the untreated control group, the initial number of 3.36 ± 0.6 MAs remained almost unchanged over 3-4 months (2.89 ± 0.57 MAs). Dynamic analysis showed that after ranibizumab treatment 3.06 ± 0.5 new MAs appeared, while 5.09 ± 0.79 disappeared. In the control group, 2.11 ± 0.4 new MAs appeared and 2.61 ± 0.48 disappeared. MA turnover was significantly higher with ranibizumab compared to the control group (8.15 ± 1.14 vs. 4.72 ± 0.81, p < 0.001). Consistently, CRT decreased from 444 to 330 µm in the ranibizumab group, while there was no change in the control group (291 vs. 288 µm). CONCLUSION: The treatment of macular edema using ranibizumab does not only reduce macular thickness, but also has an impact on the turnover of MAs in diabetic retinopathy. RetmarkerDR analysis showed that more pre-existent MAs disappeared than new MAs developed, and the absolute number of MAs also decreased.

Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy.

PURPOSE: To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs. METHODS: Two hundred and eighty-seven eyes were included in the study. Photographs obtained at Day 0, at 6, and 12 months were analyzed using the RetmarkerDR software (Critical Health SA) in a masked manner, and the MA formation rate was documented. A threshold of a calculated MA formation rate of 2 or more was chosen to consider a patient "positive." The ability to predict CSME development was then calculated for a period of up to 5 years. HbA1c values, blood pressure, or duration of diabetes were also evaluated. RESULTS: The study population consisted of 89 male and 59 female patients with a mean age of 57.6 years, a mean HbA1c of 7.8, and a mean duration of diabetes of 12.3 years. Forty-seven of 287 eyes (16.4%) developed CSME during follow-up. An increased MA formation rate of >2 MA was clearly associated with development of CSME. Using the automated analysis and a threshold of 2 or more new MA, the authors were able to identify 70.2% of the eyes that developed CSME during follow-up ("true positive") and using a threshold of up to 2 new MA, 71.7% of the patients that did not develop CSME ("true negative"). No significant differences concerning baseline and 1-year HbA1c levels within patient eyes that developed CSME compared with patient eyes below or over the calculated threshold of 2 MA (P = 0.554 and P = 0.890, respectively) were seen. The positive and negative predictive value was calculated to be 33% versus 92.5%, sensitivity was 70%, and specificity was 72%. CONCLUSION: Using the RetmarkerDR software, the authors were able to identify patients with higher risk to develop CSME during follow-up using a threshold of 2 or more MA formation rate. Together with the high negative predictive value, the automated analysis may help to determine the individual risk of a patient to develop sight-threatening complications related to diabetic retinopathy and schedule individual screening intervals.

Nonmydriatic ultra-wide-field scanning laser ophthalmoscopy (Optomap) versus two-field fundus photography in diabetic retinopathy.

The purpose of this study was to investigate the diagnostic properties of a 2-laser wavelength nonmydriatic 200° ultra-wide-field scanning laser ophthalmoscope (SLO) versus mydriatic 2-field 45° color fundus photography (EURODIAB standard) for assessing diabetic retinopathy (DR). A total of 143 consecutive eyes of patients with different levels of DR were graded regarding DR level and macular edema based on 2-field color photographs or 1 Optomap Panoramic 200 SLO image. All SLO images were nonmydriatic and all photographs mydriatic. Grading was performed masked to patient and clinical data. Based on photography, 20 eyes had no DR, 44 had mild, 18 moderate and 42 severe nonproliferative DR, and 19 eyes had proliferative DR. Overall correlation for grading DR level compared to Optomap SLO was moderate with kappa 0.54 (p < 0.001), fair-to-moderate in macular edema grading with kappa 0.39 (p < 0.001), and substantial for grading clinically significant macular edema (kappa 0.77). The wide-field SLO offers a wider field of view and can potentially better differentiate lesions by applying the 2 laser wavelengths. However, these advantages over 2-field fundus photography need to be confirmed in further studies.

Functional and morphological changes in diabetic macular edema over the course of anti-vascular endothelial growth factor treatment.

PURPOSE: To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti-vascular endothelial growth factor (VEGF) treatment with Ranibizumab. METHODS: A consecutive series of 39 study eyes with centre-involving DME were included in this study. In all subjects, best-corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD-OCT) cross-sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross-sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. RESULTS: Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 µm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = -1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = -3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = -4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = -1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = -0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = -2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. CONCLUSIONS: ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti-VEGF therapy with Ranibizumab in patients with DME.

Idebenone prevents human optic nerve head astrocytes from oxidative stress, apoptosis, and senescence by stabilizing BAX/Bcl-2 ratio.

PURPOSE: Oxidative stress plays an important role in the pathogenesis of several neurodegenerative diseases including glaucoma. Astrocytes are supposed to play a role in glaucoma pathogenesis. This study investigates the antiapoptotic and cytoprotective effects of idebenone on optic nerve head astrocytes (ONHA) under oxidative stress. METHODS: ONHA were treated with 1 to 150 µM idebenone. Cell viability (MTT assay and live-dead assay), induction of intracellular reactive oxygen species, senescence-associated ß-galactosidase activity were investigated. In addition, apoptosis (detection of histone-associated DNA fragmentation), and expression of BAX and Bcl-2, and their mRNA were determined after 48 hours and after hydrogen peroxide (H2O2) treatment. RESULTS: Idebenone concentrations from 1 to 50 µM showed no effects on ONHA viability. Pretreatment with 10 µM idebenone led to an increase in viability of ONHA after H2O2 treatment. In addition, idebenone pretreatment significantly attenuated the increase of histone-associated DNA fragmentation, induction of senescence-associated ß-galactosidase, and intracellular reactive oxygen species after treatment with H2O2. When ONHA cells were treated with idebenone and H2O2, real-time polymerase chain reaction and Western blot analysis yielded an increased expression of Bcl-2 and a decrease of BAX compared with those cells that were treated with H2O2 only. CONCLUSIONS: Idebenone reduced senescence, oxidative stress, and apoptotic cell death in cultured ONHA in vitro. Our results suggest that idebenone may help to protect ONHA in vivo, and therefore might be helpful in preventing the progression of glaucomatous degeneration.

Alterations of vascular pigment epithelium detachments associated with age-related macular degeneration during upload with intravitreal ranibizumab.

PURPOSE: To describe morphologic alterations of pigment epithelial detachments (PEDs) associated with neovascular age-related macular degeneration during anti-vascular endothelial growth factor upload therapy with ranibizumab. METHODS: Prospective, single-arm interventional study. Primary outcome was the reduction of height of PED during monthly treatment using ranibizumab. Secondary outcomes were factors influencing the regression of PED. Inclusion criteria were presence of PED associated with naive neovascular age-related macular degeneration, visual acuity of >20/200, and height of PED >150 µm on optical coherence tomography. All eyes (n = 54) received 3 injections of ranibizumab in monthly intervals ("upload therapy"). Last review examination was performed 14 weeks after the initial treatment. RESULTS: The mean PED height decreased from 515 µm (SD, 268.3) to 294 µm (SD, 201.9) at Week 14 with the highest degree of regression after the first treatment. A complete resolution of PED was noted in 8 eyes (15%). Using conventional regression model, none of the factors investigated, including height of PED, presence of intraretinal or subretinal fluid, intraretinal cysts, macular volume, retinal thickness, presence of foveal depression, presence of hemorrhage, and visual acuity, had a significant impact on the morphologic response. Using a modified binary logistic regression model ("bootstrapping"), presence of foveal depression (P > 0.033), and retinal thickness (P > 0.004) showed statistical significance. CONCLUSION: This study on the responses and potential predictive factors associated with vascularized PED during the uploading phase of intravitreal ranibizumab shows a complete resolution of the PED in 15% of the cases.

Improvement of diabetic retinopathy with intravitreal Ranibizumab.

This study indicates that in addition to the significant improvement in visual acuity and reduction of central retinal thickness in patients with center-involving diabetic macular edema, intravitreal anti-VEGF treatment with Ranibizumab may also lead to a significant stabilization or even improvement of diabetic retinopathy.

Efficacy and safety of recombinant tissue plasminogen activator and gas versus bevacizumab and gas for subretinal haemorrhage.

PURPOSE: To report the 12 months efficacy of initial intravitreal bevacizumab or intravitreal recombinant tissue plasminogen activator (rtPA) combined with expansile gas in patients with subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD). METHODS: Forty-five eyes of 45 patients with subretinal haemorrhage (1-5 disc diameters) involving the fovea secondary to neovascular AMD were evaluated retrospectively consecutively. Thirty-two eyes underwent treatment with rtPA (50 µg/0.05 ml) combined with intravitreal sulphur hexafluoride (SF6). The other 13 eyes were treated with bevacizumab (1.25 mg/0.05 ml) and SF6. Thereafter, all patients received Vascular Endothelial Growth Factor (anti-VEGF) treatment according to modified PrONTO criteria. Main outcome was change of best-corrected visual acuity (VA) at 12 months as determined by Early Treatment Diabetic Retinopathy (ETDRS). RESULTS: There was more improvement in patients initially treated with rtPA and gas (14 letters; bevacizumab and gas eight letters) and not suffering from adverse events. The incidence of vitreous haemorrhages was significantly higher in the rtPA group (nine of 32 versus one of 13, p < 0.01). In both groups, an average of 3.5 anti-VEGF injections were performed per patient during 12 months (no difference between both groups). CONCLUSION: Both initial treatment regimen lead to improved functional results after 1 year. However, patients, not suffering from adverse events, who underwent initial treatment with rtPA and gas showed better results. To maintain VA, controlling neovascular AMD by anti-VEGF treatment regime after initial treatment with rtPA+gas is important for all cases.

The therapeutic potential of intraocular depot steroid systems: developments aimed at prolonging duration of efficacy.

BACKGROUND: Corticosteroids play a major role in the treatment of many diseases of the posterior ocular segment. Systemically or topically administered steroids usually do not attain therapeutic concentrations in the retina, as they must first cross the blood-retina barrier. Intravitreal application is a useful alternative means of achieving therapeutic concentrations in the posterior segment but must be repeated every few weeks, because drugs given in this way have a short half-life. Intraocular sustained-release implants have been now developed in order to prolong the effect of intravitreal drugs and to lessen the need for repeated application. Macular edema is a typical indication for intravitreal steroid treatment. METHODS: Selective review of the literature. RESULTS: Various intravitreal corticosteroid implants have been evaluated in prospective, randomized clinical trials in recent years, and some have been approved for clinical use. Implants are either longer-acting and non-resorbable (fluocinolone acetonide implants) or shorter-acting and resorbable (dexamethasone implants). Major adverse effects of intravitreal corticosteroids include the induction or worsening of cataracts and elevated intraocular pressure. The likelihood of a complication varies from implant to implant and depends on the duration of action of the particular one used. CONCLUSION: Intravitreal corticosteroid implants are a new option in the treatment of diseases of the posterior ocular segment. Long-term results are not yet available. The optimal treatment for these diseases will need to be the focus of further clinical research.

Comparison of intravitreal bevacizumab upload followed by a dexamethasone implant versus dexamethasone implant monotherapy for retinal vein occlusion with macular edema.

PURPOSE: To compare the efficacy and safety of three intravitreal bevacizumab upload injections followed by a dexamethasone implant versus dexamethasone implant monotherapy in eyes with macular edema due to retinal vein occlusion. METHODS: Sixty-four eyes of 64 patients were included in this prospective, consecutive, nonrandomized case series: group 1 consisted of 38 patients (22 with central retinal vein occlusion, CRVO, 16 with branch retinal vein occlusion, BRVO) treated using a dexamethasone implant (Ozurdex) alone; group 2 consisted of 26 patients (14 CRVO, 12 BRVO) treated with three consecutive intravitreal bevacizumab injections at monthly intervals followed by a dexamethasone implant. In case of recurrence, both cohorts received further dexamethasone implants. Preoperatively and monthly best corrected visual acuity (BCVA, ETDRS), central retinal thickness (Spectralis-OCT), intraocular pressure, and wide-angle fundus photodocumentation (Optomap) were performed. The primary clinical endpoint was BCVA at 6 months after initiation of therapy. Secondary endpoints were central retinal thickness and safety of the therapy applied. RESULTS: In group 1, an increase in BCVA of 2.5 (±1.6) letters in the CRVO and of 13.0 (±3.2) letters in BRVO patients was seen after 6 months, in group 2 of 5.9 (±0.4) letters (CRVO) and 3.8 (±2.4) letters (BRVO), which was not statistically significant. When comparing the two treatment groups with respect to the type of vein occlusion, there was a significant advantage for BRVO patients for the dexamethasone implant monotherapy (BRVO patients in group 1, p = 0.005). Central retinal thickness showed a significant reduction after 6 months only in patients of group 1, both for CRVO (p = 0.01) and BRVO (p = 0.003). First recurrence after the first dexamethasone implant injection occurred after 3.8 months (mean) in CRVO and 3.5 months in BRVO patients (group 1), versus 3.2 and 3.7 months, respectively, in group 2. In group 1, 63.6% with CRVO and 50% with BRVO showed an increased intraocular pressure after treatment; in group 2, 57.1% with CRVO and 50.0% with BRVO, respectively. CONCLUSION: In CRVO, there was no difference between the two treatment strategies investigated. However, in BRVO, dexamethasone implant monotherapy was associated with better functional outcome.