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. Copyright (C) 2012 S. Karger AG, Base

Evaluating the interreader agreement and intrareader reproducibility of Visual Field Defects in Thyroid Eye Disease- Compressive Optic Neuropathy

PURPOSE To categorize visual field (VF) defects according to Freitag and Tanking's (FT) classification in Thyroid Eye Disease-Compressive Optic Neuropathy (TED-CON) and evaluate the interreader agreement and intrareader reproducibility of the classification. SUBJECTS AND METHODS In this retrospective, observational study we included medical reports of 96 eyes (51 patients), who underwent VF testing with TED-CON in Ludwig-Maximilians-University (2008-2019). Two readers separately examined the VFs at the time of the TED-CON diagnosis, each offering two readings of the same VF in a time interval of 1 month. None of our patients were diagnosed with only VF testing. The visual field testing was only performed when the inclusion criteria for TED-CON were met. RESULTS The most common VF defects upon TED-CON diagnosis were stage 1b defects in FT classification (34.4% for reader 1, 35.4% for reader 2), followed by stage 2b (10.4% for reader 1, 14.6% for reader 2), and stage 3 (10.4% for both readers). The overall interreader agreement between 2 examiners was substantial for the first reading (69.8% agreement, kappa 0.635 (95% CI 0.525-0.745)) and moderate for the second reading (66.7{\%} agreement, kappa 0.598 (95{\%} CI 0.488-0.708)). The intrareader reproducibility ranged from substantial to almost perfect (78.1{\%} agreement) between readings (kappa 0.736 (95{\%}CI 0.638-0.834)) for reader 1 and 90.6{\%} agreement (kappa 0.885 (95{\%}CI 0.814-0.956)) for reader 2. CONCLUSION We found good BCVA (LogMAR $\leq$ 0.2), in nearly half of the cases (44 eyes, 45.8{\%}) and also, strikingly near perfect visual acuity (BCVA LogMAR $\leq$0.1) in 22.9{\%} of the cases (22 eyes) with TED-CON. We conclude that clinicians should be alert to VF defects in the inferior region (stage 1a/1b in the FT classification) even in patients with a good BCVA

Microbial keratitis-induced endophthalmitis: incidence, symptoms, therapy, visual prognosis and outcomes

Background: To evaluate symptoms, therapies and outcomes in rare microbial keratitis-induced endophthalmitis. Methods: Retrospective study with 11 patients treated between 2009 and 2014. Clinical findings, corneal diseases, history of steroids and trauma, use of contact lenses, number and type of surgical interventions, determination of causative organisms and visual acuity (VA) were evaluated. Results: The incidence of transformation from microbial keratitis to an endophthalmitis was 0.29% (n = 11/3773). In 90.9% (n = 10/11), there were pre-existent eyelid and corneal problems, in 45.5% (n = 5/11) rubeosis iridis with increased intraocular pressure and corneal decompensation, and in 18.2% (n = 2/11), ocular trauma. Specimens could be obtained in 10 of 11 samples: 33.3% of those 10 specimens were Gram-positive coagulase-negative Staphylococci (n = 3/10) or Gram-negative rods (n = 3/10) and 10.0% Staphylococcus aureus (n = 1/10). In 30% (n = 3/10), no pathogens were identifiable. 72.7% (n = 8/11) of all keratitis-induced endophthalmitis were treated with vitrectomy and 9.1% (n = 1/11) with amniotic-membrane transplantation. In 27.3% (n = 3/11) the infected eye had to be enucleated – 18.2% (n = 2/11) primarily, 9.1% (n = 1/11) secondarily. No patient suffered from sympathetic ophthalmia. The median initial VA was 2.1 logMAR (n = 11/11). At one month, median VA was 2.0 logMAR (n = 7/11), after three months 2.0 logMAR (n = 6/11), and after one year 2.05 logMAR (n = 6/11). The change in VA was not significant (p > 0.99). 36.4% (n = 4/11) of the cases resulted in blindness. Conclusions: The overall outcome is poor. Enucleation should be weighed against the risk of local and systemic spread of the infection, prolonged rehabilitation and sympathetic ophthalmia

A pathological indicator for dysthyroid optic neuropathy: tritan color vision deficiency

PURPOSE To investigate the sensitivity of the color vision test by Arden in patients with dysthyroid optic neuropathy (DON) to improve diagnosis. METHODS In this observational, retrospective study, we included the medical records of 92 eyes (48 patients) with diagnosis of DON between 2008 and 2019 in order to evaluate the full spectrum of findings from the color vision test by Arden, and to determine potential importance of this test. Thirty-five patients were female, and 13 patients were male. The mean age was 58.0~years (range: 34-79) at the time of the DON diagnosis. RESULTS Forty-one eyes displayed relatively good BCVA with ≤ 0.2 LogMAR. We found a protan value exceeding the threshold of ≥ 8% in 57 eyes (30 patients) at the time of the diagnosis. The sensitivity of protan was 61.9% (95% CI 51.2-71.8%), while that of tritan was a striking 98.9% (95% CI 94.1-99.9%). We discovered one pathological sign, tritan deficiency (based on a threshold of ≥ 8%) consistently in all eyes but one at the time of the diagnosis, regardless of the visual field defects or any changes in best-corrected visual acuity (BCVA). CONCLUSION We found blue-yellow (tritan) deficiency, to be a sensitive and reliable indicator of dysthyroid optic neuropathy. We conclude that, in cases with suspected DON, a color vision test that can detect tritan deficiency is an essential tool for the adequate assessment, diagnosis, and treatment of DON

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

Background: To evaluate the fulfilment 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 mm 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 mu m and decreased significantly (p<0.001) by 71.22 +/- 106.93 to 206.85 +/- 60.30 mu m. Evaluation of the fulfilment 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 mu m), but the morphological retreatment criteria (CRT increase of 100 mu m 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 mm or more) appear to be not sensitive enough in a clinical setting with referring ophthalmologists

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

Background: To evaluate the fulfilment 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 mm 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 mu m and decreased significantly (p<0.001) by 71.22 +/- 106.93 to 206.85 +/- 60.30 mu m. Evaluation of the fulfilment 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 mu m), but the morphological retreatment criteria (CRT increase of 100 mu m 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 mm or more) appear to be not sensitive enough in a clinical setting with referring ophthalmologists

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

Multimodal imaging in acute retinal ischemia: spectral domain OCT, OCT-angiography and fundus autofluorescence

AIM: To describe retinal findings of various imaging modalities in acute retinal ischemia. METHODS: Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), OCT-angiography (OCT-A) and fundus autofluorescence (FAF) images of 13 patients (mean age 64y, range 28-86y) with acute retinal ischemia were evaluated. Six suffered from branch arterial occlusion, 2 had a central retinal artery occlusion, 2 had a combined arteriovenous occlusions, 1 patient had a retrobulbar arterial compression by an orbital haemangioma and 2 patients showed an ocular ischemic syndrome. RESULTS: All patients showed increased reflectivity and thickening of the ischemic retinal tissue. In 10 out of 13 patients SD-OCT revealed an additional highly reflective band located within or above the outer plexiform layer. Morphological characteristics were a decreasing intensity with distance from the fovea, partially segmental occurrence and manifestation limited in time. OCT-A showed a loss of flow signal in the superficial and deep capillary plexus at the affected areas. Reduced flow signal was detected underneath the regions with retinal edema. FAF showed areas of altered signal intensity at the posterior pole. The regions of decreased FAF signal corresponded to peri-venous regions. CONCLUSION: Multimodal imaging modalities in retinal ischemia yield characteristic findings and valuable diagnostic information. Conventional OCT identifies hyperreflectivity and thickening and a mid-retinal hyperreflective band is frequently observed. OCT-A examination reveals demarcation of the ischemic retinal area on the vascular level. FAF shows decreased fluorescence signal in areas of retinal edema often corresponding to peri-venous regions

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT