Identification of Dietzia Species in a Patient with Endophthalmitis following Penetrating Injury with Retained Intraocular Metallic Foreign Body

To the best of our knowledge, we report the first case of Dietzia species in a patient with endophthalmitis. A 47-year-old man presented to the ophthalmology department with decreased vision, redness, and minimal pain in his right eye after a foreign body struck his eye following working using a hammer and chisel. Broad-spectrum polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) sequencing targeting 16S ribosomal ribonucleic acid-(rRNA-) encoding gene on an undiluted vitreous sample revealed 100% identity with GenBank sequences of Dietzia species including D. natronolimnaea, D. dagingensis, and D. cercidiphylli. The culture of the vitreous samples demonstrated the growth of Gram-positive cocci and polymorphic rods. The isolate from the culture was identified as D. natronolimnaea using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). The combination of surgical and medical treatment (pars plana vitrectomy and systemic and topical antibiotics) eradicated the infection successfully

Macular Hole Surgery Using Gas Tamponade—An Outcome from the Oslo Retrospective Cross-Sectional Study

Purpose: The study aims to determine the anatomical success and functional outcome of pars plana vitrectomy (PPV) for macular holes (MH) performed at a single study center using a consistent procedure of internal limiting membrane (ILM) peeling, SF6 tamponade and 3 days face-down positioning. Methods: A retrospective cross-sectional study involving eyes with MHs which underwent 23- or 25-gauge PPV with or without phacoemulsification and all undergoing a 20% SF6 gas tamponade, follow-up to 6 months postoperatively were included at the Department of Ophthalmology, Oslo University Hospital and University of Oslo, Oslo, Norway (12-month study period between 1 January and 31 December 2015) Pre- and post-operative Best-Corrected Visual Acuity (BCVA) assessment, comprehensive eye examination and intraocular pressure (IOP) measurement. as well as Optical Coherence Tomography to determine the diameter of the MH and its closure were all carried out. Results: 198 consecutive eyes operated for MH (age: 69.4 ± 7.6 years; 1.6:1 female:male ratio) were included; 35.7%/48.6% had symptoms from 3–6/6–48 months; 5.1% had high-grade myopia, 21.5% focal VMT <1500 µm with or without epiretinal membrane (ERM), and 74.0%/26.0% had phakic/pseudophakic status. Primary closure of the MH occurred in 93.3% of the patients. Lens status and length of symptoms showed no significant correlation with closure of the MH. The pre-operative logMAR visual acuity: 0.8 ± 0.3 (median: 0.7; interquartile range (IQR): 0.5–0.8; range: 0.3–1.7), improved significantly post-operatively: 0.4 ± 0.3 (median: 0.3; interquartile range (IQR): 0.1–0.5; range: −0.02–1.2). BCVA improvement of <0.2, 0.2–0.4 and >0.4 was present in 28.3%, 27.3% and 44.4% of the treated patients. No significant median differences could be detected between the duration of the pre-operative symptoms and the pre-/post-operative visual acuity. Increased IOP was measured in 2.6% of the cases day after surgery. Conclusions: Our study found visual outcome not to be dependent upon the length of symptoms in MH patients treated by PPV all undergoing ILM peeling, SF6 tamponade and face-down positioning. The large diameter MH was not a limiting factor to achieve improved post-operative BCVA

Switching to aflibercept versus continuing bevacizumab for treatment-resistant neovascular age-related macular degeneration: a one-year comparative observational study

Purpose To compare outcomes of a treatment algorithm that allows for switching treatment-resistant neovascular age-related macular degeneration (nAMD) eyes to aflibercept with continuing bevacizumab. Methods Retrospective study of nAMD patients who initiated treatment in 2012 (aflibercept unavailable) and 2018 (aflibercept available). Eyes were included in the case of residual macular fluid after a minimum of 4 monthly bevacizumab injections. Only eyes in the 2018 group could then switch to aflibercept. Results The study included 40 eyes from 2012 and 88 eyes from 2018. Patient characteristics were similar across the groups at baseline and 4 months. In 2018, 59 eyes (67%) were switched to aflibercept after 4 months. Mean change in BCVA from 4 months to one year was +2.8 letters in 2018 versus −1.7 letters in 2012 (p = 0.043). Mean change in BCVA from baseline to one year was +9.4 letters in 2018 (p < 0.001) and +4.4 letters in 2012 (p = 0.073). Mean change in CRT from 4 months to one year was −36 µm in 2018 versus −23 µm in 2012 (p = 0.373). Mean change in CRT from baseline to one year was −100 µm in 2018 (p < 0.001) and −75 µm in 2012 (p < 0.001). Mean number of injections given in one year was 11.8 in 2018 versus 10.4 in 2012 (p < 0.001). After one year, a majority of eyes in both groups still received treatment at 4-week intervals. Conclusion The study suggests that the possibility of switching eyes with treatment-resistant nAMD to aflibercept leads to a modest visual benefit compared with continuing first-line bevacizumab therapy

Inherited retinal disease in Norway - a characterization of current clinical and genetic knowledge

Purpose The purpose of this study was to characterize current clinical and genetic knowledge of patients with inherited retinal disease in Norway and give an estimate of the prevalence. These data are necessary to identify patients eligible for new personalized medicines, to facilitate genetic counselling for their families and to plan clinical follow‐up. Methods A patient registry including clinical and genetic data was established. Clinical data were retrieved during 2003–2018. Genetic testing was performed in the period 2007–2018. Results The material included 866 patients with 41 clinical diagnoses at the cut‐off date. The most prevalent diseases were as follows: retinitis pigmentosa (54%), Stargardt macular dystrophy (6.5%) and Leber congenital amaurosis (5.2%). A genetic diagnosis was identified in 32% of patients. In total, 207 disease‐causing variants in 56 genes were reported. The most commonly reported disease‐causing genes were ABCA4, USH2A and BEST1. The estimated adjusted minimum prevalence of inherited retinal disease in the south‐east region of Norway was 1: 3,856 (2.6/10 000). Conclusion This population‐based study demonstrated an estimated prevalence for all inherited retinal diseases in south‐east Norway and described the distribution of clinical diagnoses, onset of symptoms, inheritance patterns and genetic data and thereby expands our knowledge of inherited retinal disease in Norway. The newly established registry and biobank will support patient feasibility for future clinical trials, treatment selection and counselling of families

Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys). Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure. Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3. Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa

Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys). Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure. Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3. Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa

Does pharmaceutical compounding of vascular endothelial growth factor inhibitors for intravitreal use alter the risk of post-injection endophthalmitis?

Purpose To investigate the safety of pharmaceutically compounded syringes for intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) drugs. Methods Single center, retrospective chart review. From 2015 to 2019, Oslo University Hospital, Norway gradually implemented pharmaceutical compounding and splitting of bevacizumab, ranibizumab, and aflibercept vials into multiple prefilled syringes for intravitreal use. Medical records of all post-injection endophthalmitis (PIE) cases in this 5-year period were reviewed. The incidences of PIE associated with compounded and clinician-withdrawn syringes were compared. Results In 5 years, the total number of anti-VEGF injections was 112,926; 68,150 procedures (60%) utilized compounded syringes, and 44,776 procedures (40%) utilized clinician-withdrawn syringes. A total of 11 PIE cases were identified (incidence 0.10 per 1000; 95% CI 0.05–0.17). Five PIE cases were associated with compounded syringes (incidence 0.07 per 1000; 95% CI 0.03–0.17); 3 of these were culture positive. Six PIE cases were associated with clinician-withdrawn syringes (incidence 0.13 per 1000; 95% CI 0.06–0.29); 2 of these were culture positive. The relative risk of PIE following procedures utilizing compounded versus clinician-withdrawn syringes was 0.55 (95% CI 0.17–1.79; p = 0.32). Conclusion Use of compounded anti-VEGF drugs in a large clinical setting was not associated with an altered risk of PIE. The finding adds to the evidence that splitting of vials into prefilled syringes for intravitreal injections is safe, provided that an appropriate pharmaceutical compounding procedure is strictly followed

Thirteen years of intravitreal anti-vascular endothelial growth factor therapy: the promises and burdens of a paradigm shift told from the perspective of the largest retina service in Norway

Purpose To describe the first 13 years of anti‐vascular endothelial growth factor (anti‐VEGF) therapy from the perspective of a public ophthalmic department serving a local community of almost one million people. Methods Retrospective registry study. Data from Oslo University Hospital, Norway were collected from 2006 through 2018. Hospital episode statistics were searched for episodes of care encompassing intravitreal anti‐VEGF procedures. Patient‐specific ID numbers, diagnoses, and drug codes were registered. In general, bevacizumab was used as first‐line treatment, with aflibercept reserved for resistant cases from 2013. Results The number of unique patients treated per year increased from 130 in 2006 to 3428 in 2018. In 2018, 2488 (73%) patients had also received treatment the previous year. The number of yearly injections increased from 228 in 2006 to 25 570 in 2018. In 2018 the diagnosis macular degeneration constituted 69% of injections, diabetic retinopathy constituted 15%, retinal vein occlusion constituted 13%, and other diagnoses constituted 3%. In the same year 49% of injections were with bevacizumab, 46% with aflibercept, 4% with ranibizumab, and 1% with dexamethasone implants. The bevacizumab to aflibercept ratio was almost 1:1 for macular degeneration and diabetic retinopathy; for retinal vein occlusion the ratio was 13:7. Conclusion In 13 years there was an approximately 100‐fold increase in the number of yearly intravitreal injections. A majority of patients received long‐term treatment. Macular degeneration was the most common diagnosis. Using bevacizumab as first‐line treatment, with aflibercept reserved for resistant cases from 2013, eventually resulted in a nearly 1:1 ratio in drug usage

Intraoperative Optical Coherence Tomography in the Management of Macular Holes: State of the Art and Future Perspectives

Background: Non-invasive diagnostic technologies in ophthalmology have substantially transformed contemporary clinical practice. Intraoperative optical coherence tomography (iOCT) systems have recently been used for various surgical interventions, including the treatment of full-thickness macular holes (FTMHs). Materials and Methods: We conducted a systematic review on the use of iOCT and its possible benefits in the management of FTMHs, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, were assessed for all included articles. Results: 1131 articles were initially extracted, out of which 694 articles were obtained after duplicates were removed and their abstracts screened. A total of 65 articles was included for full-text review. Finally, 17 articles remained that fulfilled the inclusion criteria. Conclusions: Even though there is just a small number of studies with solid results, the use of iOCT in FTMH surgery may be a helpful tool for both novice and experienced surgeons planning and managing difficult cases. Additionally, it could be used for teaching reasons and for exploring novel surgical techniques