Five-Year Risk and Safety Profile of Autologous Serum Eye Drop Therapy.

PURPOSE: To evaluate the risk and safety profile of autologous serum eye drop therapy in clinical routine over a period of 5 years. METHODS: This retrospective study involved all patients treated with autologous serum between July 2014 and December 2019 at a tertiary ophthalmic referral center. The electronic patient record system was searched for all patients with autologous serum eye drop therapy at any time point. These records were subsequently searched for keywords such as infectious keratitis, corneal ulcer, conjunctivitis, or endophthalmitis at any recorded contact. The probability of an association between the therapy with autologous serum eye drops and infectious complications was investigated independently by three corneal specialists and rated as likely, potential, or unlikely. RESULTS: In total, 752 patients were treated with autologous serum eye drops between July 2014 and December 2019. There were 5 384 batches with a total of 107 680 bottles of serum eye drops that had been produced and dispensed for these patients during this period. The records of 291 patient showed a combination of autologous serum therapy and at least one keyword for infectious diseases. In 288 patients, individual case analyses revealed an unlikely association between the therapy and infection, as their infectious episodes occurred either before the start of the therapy, more than 1 month after the therapy ceased, or in the contralateral untreated eye in the case of unilateral therapy. Three cases of infectious keratitis were classified as potentially associated with autologous serum therapy. However, all three patients suffered from chronic anterior eye diseases with a high risk of spontaneous infectious complications independent of therapy with autologous eye drops. None of the infectious events was rated as being likely due to the serum eye drops. CONCLUSIONS: Serum eye drops are often used in patients with severe or chronic anterior eye diseases with an intrinsic risk of infectious diseases. Despite these preexisting risk factors, autologous serum eye drops can be considered safe, even in patients with a compromised ocular surface.

Bilateral blindness after uneventful brolucizumab injection for macular degeneration.

BACKGROUND: We report a very severe case of bilateral panuveitis and ischemic vasculitis with possible perineural inflammation, which followed bilateral intravitreal brolucizumab administration in a patient with neovascular age-related macular degeneration (nAMD). CASE PRESENTATION: On December 11, 2020, a 81-year-old woman presented with severe bilateral loss of vision. Eight days earlier, she had received uneventful bilateral injection of brolucizumab, a novel anti-vascular endothelial growth factor (VEGF) single-chain variable region (scFv) recombinant protein drug, for treatment of neovascular age-related macular degeneration (nAMD). Slit-lamp examination revealed signs of a bilateral panocular vasculitis with ischemia. Scanning laser ophthalmoscopy of her left eye revealed marked vascular sheathing. T1 fat-saturated post-contrast images of the orbit revealed a higher-than-normal signal of the choroid, with localized choroidal detachment. Additionally, pathologic enhancement was visible around the optic nerve in the orbit, which was interpreted as vasculitis. Due to the severe bilateral panuveitis with vasculitis, an additional vitreous tap was obtained, which revealed elevated levels of interleukin six and interleukin ten. CONCLUSIONS: To our knowledge, this is the first documented case showing both panuveitis and ischemic vasculitis with possible perineural inflammation. We do not recommend performing bilateral brolucizumab injections until more data is available regarding the mechanism of brolucizumab-induced vasculitis. From a clinical point of view, we find it difficult to justify the use of brolucizumab when there are other well-known agents, such as ranibizumab and aflibercept, which have better safety profiles and comparable efficacy.

Occurrence of motility disorders in patients undergoing tube surgery-consecutive, retrospective follow-up case series analysis.

BACKGROUND: The two glaucoma drainage devices (GDD) Ahmed and Baerveldt tubes are most commonly used for the treatment of refractory glaucoma. We noticed a significant number of patients with postoperative motility disorders resulting in diplopia. We investigated the occurrence and patterns of postoperative motility disorders overall and between the two GDD tubes using the Hess Screen Test. METHODS: Retrospective single-center matched case series of 20 patients undergoing Ahmed and 20 patients undergoing Baerveldt tube implantation with a follow-up of at least 1 year. In order to investigate the dynamic of GDD-induced motility disorder over time, from 25 patients, a follow-up examination from two different time periods (3 to 6 months and 12 to 24 months postoperatively) was available. From these 25 patients, 12 had received an Ahmed and 13 a Baerveldt GDD. To compare the different Hess Screen Tests, we developed nine categories of possible emerging motility disorder in the operated eye as a primary endpoint: Motility restriction in up-gaze, in down-gaze, in abduction, in adduction; combined motility disorders in up-gaze and adduction, up-gaze and abduction, down-gaze and adduction, down-gaze and abduction. If there was no motility disorder, this was also separately classified. RESULTS: Regardless of the used device, Ahmed or Baerveldt, most patients experienced motility disorders to some extent; mainly down-gaze and adduction were affected. However not every motility disorder resulted in diplopia. Although over time a decrease in ocular misalignment was seen, the incidence of diplopia was stable. Nevertheless, only few required therapy. We noted no difference between Ahmed and Baerveldt tube implant devices. CONCLUSION: Ocular misalignment and restriction of motility is a common finding after GDD. Although not every motility disorder results in diplopia, it is frequent. Therefore, it needs to be taken into consideration in informed consent.

Don't be afraid of the dark - OCT angiography through a black intraocular lens.

PURPOSE: To report a case in which optical coherence tomography (OCT) and OCT angiography (OCT-A) allowed imaging of the posterior pole in a patient fitted with a black occlusive intraocular lens (IOL). OBSERVATIONS: Following retinal central artery occlusion, a 52-year-old patient suffered from disturbing residual light perception. Occlusive contact lenses blocked the light insufficiently, so that the patient had to rely on an eye patch for relief of symptoms. After no neovascularization had formed during an observation period of 12 months, a black IOL (Morcher 85F) was implanted, blocking wavelengths in the visible spectrum but allowing transmission in the near-infrared spectrum. Slit lamp photography, OCT and OCT-A were performed pre- and postoperatively. Postoperatively, slit lamp photography could no longer provide images of the posterior pole, proving the effective blockade of wavelengths in the visible light spectrum. In contrast, transmission in the near-infrared spectrum allowed for OCT and OCT-A imaging of the fundus. The complete suppression of the disturbing perception of light succeeded only temporarily. CONCLUSIONS AND IMPORTANCE: The implantation of a black IOL does not prevent the imaging of the retinal microvasculature by OCT-A. Black IOLs can therefore be considered even if continued monitoring of the vascular situation of the posterior pole is required.

Evidence assessing the diagnostic performance of medical smartphone apps: a systematic review and exploratory meta-analysis.

OBJECTIVE: The number of mobile applications addressing health topics is increasing. Whether these apps underwent scientific evaluation is unclear. We comprehensively assessed papers investigating the diagnostic value of available diagnostic health applications using inbuilt smartphone sensors. METHODS: Systematic Review-MEDLINE, Scopus, Web of Science inclusive Medical Informatics and Business Source Premier (by citation of reference) were searched from inception until 15 December 2016. Checking of reference lists of review articles and of included articles complemented electronic searches. We included all studies investigating a health application that used inbuilt sensors of a smartphone for diagnosis of disease. The methodological quality of 11 studies used in an exploratory meta-analysis was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool and the reporting quality with the 'STAndards for the Reporting of Diagnostic accuracy studies' (STARD) statement. Sensitivity and specificity of studies reporting two-by-two tables were calculated and summarised. RESULTS: We screened 3296 references for eligibility. Eleven studies, most of them assessing melanoma screening apps, reported 17 two-by-two tables. Quality assessment revealed high risk of bias in all studies. Included papers studied 1048 subjects (758 with the target conditions and 290 healthy volunteers). Overall, the summary estimate for sensitivity was 0.82 (95 % CI 0.56 to 0.94) and 0.89 (95 %CI 0.70 to 0.97) for specificity. CONCLUSIONS: The diagnostic evidence of available health apps on Apple's and Google's app stores is scarce. Consumers and healthcare professionals should be aware of this when using or recommending them. PROSPERO REGISTRATION NUMBER: 42016033049.

Contralesional Trunk Rotation Dissociates Real vs. Pseudo-Visual Field Defects due to Visual Neglect in Stroke Patients.

In stroke patients, the clinical presentation of visual field defects (VFDs) is frequently accompanied by visual neglect, i.e., the inability to attend and respond to the contralesional space. However, the diagnostic discrimination between the lack of reactions to contralesional stimuli due to VFDs or visual neglect is challenging during clinical examination. This discrimination is particularly relevant, since both clinical pictures are associated with different therapeutic approaches and outcomes. The aim of this study was to systematically investigate the effectiveness of trunk rotation toward the contralesional side-a manipulation dissociating the coordinate system of the trunk from that of the head and eyes-in disentangling real VFDs from "pseudo-VFDs" that occur due to visual neglect. Twenty patients with a left-sided VFD after a right-hemispheric stroke (10 additionally showing visual neglect in neuropsychological testing, VFD + neglect; 10 without neglect, VFD) were tested with Goldmann perimetry in both standard and trunk rotation conditions. In the standard condition, both VFD and VFD + neglect patients showed a conspicuous narrowing of the left visual field. However, trunk rotation triggered strikingly different patterns of change in the two groups: it elicited a significant increase in visual field extension in the VFD + neglect group, but left visual field extension virtually unchanged in the VFD group. Our results highlight contralesional trunk rotation as a simple, viable manipulation to effectively and rapidly disentangle real VFDs from "pseudo-VFDs" (i.e., due to visual neglect) during clinical examination.

Efficacy and adverse events of aflibercept, ranibizumab and bevacizumab in age-related macular degeneration: a trade-off analysis.

TOPIC: To quantify the gain in visual acuity and serious side effects of ranibizumab, bevacizumab and aflibercept in age-related macular degeneration (AMD). CLINICAL RELEVANCE: There is an ongoing debate about the optimal treatment of AMD with these three antivascular endothelial growth factor (anti-VEGF) treatments. METHODS: Network meta-analyses. (Pre)Medline, EMBASE, SCOPUS, Cochrane Library (until April 2013), Science Citation Index and reference lists were searched for placebo-controlled randomised trials or head-to-head comparisons. Outcomes were 1-year follow-up data of visual acuity (letters gained) and serious (vascular death, any death, stroke, myocardial infarction, transient ischaemic attack) and thrombotic events. Two investigators independently assessed eligibility and quality of included studies and extracted data. RESULTS: 11 trials (enrolling 8341 patients) assessing five active treatments were included. Compared with placebo, all anti-VEGF treatments had a significantly higher percentage of letters gained: ranibizumab 0.3 mg 2.39% (95% CI 1.59 to 3.19; p<0.001), ranibizumab 0.5 mg 3.56% (95% CI 2.58 to 4.13; p<0.001), bevacizumab 1.25 mg 2.14% (95% CI 0.47 to 3.82; p=0.012), aflibercept 0.5 mg 2.91% (95% CI 0.99 to 4.82; p=0.003) and aflibercept 2 mg 3.44% (95% CI 1.73 to 5.14; p<0.001). Compared with placebo, serious side effects were higher in all other treatments: ranibizumab 0.3 mg 4.41% (95% CI 3.42 to 5.40; p<0.001), ranibizumab 0.5 mg 5.33% (95% CI 4.37 to 6.30; p<0.001), bevacizumab 1.25 mg 5.58% (95% CI 3.567 to 7.60; p<0.001), aflibercept 0.5 mg 5.65% (95% CI (3.28 to 8.02; p<0.001) and aflibercept 2 mg 5.29% (95% CI 3.18 to 7.39; p<0.001). Compared with placebo, systemic thrombotic events also occurred more often in all other treatments. CONCLUSIONS: The study revealed only a modest superiority of aflibercept 2 mg and ranibizumab 0.5 mg over other formulations and dosages.

Assessing the efficacy of the electronic patient record system EDeR: implementation study--study protocol.

INTRODUCTION: Despite many innovations in information technology, many clinics still rely on paper-based medical records. Critics, however, claim that they are hard to read, because of illegible handwriting, and uncomfortable to use. Moreover, a chronological overview is not always easily possible, content can be destroyed or get lost. There is an overall opinion that electronic medical records (EMRs) should solve these problems and improve physicians' efficiency, patients' safety and reduce the overall costs in practice. However, to date, the evidence supporting this view is sparse. METHODS AND ANALYSIS: In this protocol, we describe a study exploring differences in speed and accuracy when searching clinical information using the paper-based patient record or the Elektronische DateneRfassung (EDeR). Designed as a randomised vignette study, we hypothesise that the EDeR increases efficiency, that is, reduces time on reading the patient history and looking for relevant examination results, helps finding mistakes and missing information quicker and more reliably. In exploratory analyses, we aim at exploring factors associated with a higher performance. ETHICS AND DISSEMINATION: The ethics committee of the Canton Lucerne, Switzerland, approved this study. We presume that the implementation of the EMR software EDeR will have a positive impact on the efficiency of the doctors, which will result in an increase of consultations per day. We believe that the results of our study will provide a valid basis to quantify the added value of an EMR system in an ophthalmological environment.

Penetration of a topically administered anti-tumor necrosis factor alpha antibody fragment into the anterior chamber of the human eye.

OBJECTIVE: To determine whether topically applied ESBA105, a single-chain antibody fragment against tumor necrosis factor (TNF)-α, could efficiently penetrate into the anterior chamber of the human eye. DESIGN: Multicenter, interventional cohort study. PARTICIPANTS: Otherwise healthy patients undergoing cataract surgery (cohorts I-III) or combined cataract surgery and vitrectomy (cohort IV). METHODS: ESBA105 (n = 57) or placebo (n = 22) was preoperatively applied as eye drops to 1 eye in patients scheduled for cataract surgery (n = 73) or combined cataract surgery and vitrectomy (n = 6). ESBA105 was administered on the day of surgery at 1-hour intervals (last dose 1 hour preoperatively) as 1.6 mg in 4 drops for cohort I (n = 15) and as 3.2 mg in 8 drops for cohorts II (n = 15) and IV (n = 6). Cohort III (n = 43) was randomized 1:1 in double-masked fashion to receive either ESBA105 6.4 mg or placebo over 4 days using 4 drops per day at 4-hour intervals (last dose 12 hours preoperatively). Aqueous humor (all cohorts), vitreous humor (cohort IV only), and blood samples (all cohorts) were collected for measurement of ESBA105. MAIN OUTCOME MEASURES: ESBA105 intraocular concentration. RESULTS: Both 4 times daily over 4 days dosing (cohort III) and 8 times daily dosing (cohorts II and IV) resulted in reliably high ESBA105 concentrations in aqueous humor. Mean molar excess of intraocular ESBA105 over its target (intraocular TNF-α) was calculated as 96-fold (cohort III) to 359-fold (cohorts II and IV). Results from the cohorts receiving 4 and 8 hourly drops per 1 day (cohorts I, II, and IV) indicated that dose-dependent intraocular concentrations of ESBA105 were achieved within hours of dosing. After 8 times daily dosing, 5 of 6 vitreous samples (cohort IV) had undetectable ESBA105 levels. ESBA105 was detected in 17 of 55 preoperative serum samples but no longer detectable in serum 1 day after surgery (0 of 19 samples). In cohort III, treatment-emergent adverse events were identical between ESBA105 and placebo groups (2 cases each of eye irritation). CONCLUSIONS: These results demonstrate that the topically applied single-chain antibody fragment ESBA105 penetrated into the anterior chamber of the human eye at therapeutic levels.

Comparison and reproducibility of corneal thickness and curvature readings obtained by the Galilei and the Orbscan II analysis systems.

PURPOSE: To compare central corneal thickness (CCT) and keratometry readings using the Galilei dual Scheimpflug analyzer, the Orbscan II anterior segment analysis system, and the Sonogage ultrasound (US) pachymeter. SETTING: Lucerne Eye Clinic, Cantonal Hospital, Lucerne, Switzerland. METHODS: In a prospective single-center study, 85 eyes of 45 healthy volunteers were examined with the Orbscan II and Galilei systems in random order followed by Sonogage US pachymetry. The CCT and keratometry measurements were compared using a paired t test. To assess the intraobserver and interobserver reproducibility of the 2 keratometers, 9 volunteers were examined 3 times by 4 independent observers and the intraclass correlation coefficient (ICC) was calculated. RESULTS: The mean CCT was 551.7 microm+/-36.6 (SD) with the Galilei, 554.8+/-45.1 microm with the Orbscan II, and 558.5+/-38.4 microm with the Sonogage. The CCT readings of the Galilei and Orbscan II did not differ significantly (P= .12). The mean keratometry readings with the Galilei and Orbscan II were similar, although both the steep (Ks) and flat (Kf) axes tended to be flatter with the Galilei system. The ICCs for CCT, Kf, and Ks were high with both keratometers (0.98, 0.97, 0.84 for Galilei and 0.97, 0.96, 0.95 for Orbscan II, respectively), indicating that variation in measurements was mainly due to true subject-to-subject variation rather than observer error. CONCLUSION: Keratometry and pachymetry readings with the Galilei and Orbscan II systems showed good concordance and high reproducibility, which would allow the examinations to be delegated to nonmedical personnel.

Combined pars plana vitrectomy and phacoemulsification with intraocular lens implantation in severe proliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVE: To evaluate the results of combined vitrectomies and intraocular lens implantations in cases of proliferative diabetic retinopathy. PATIENTS AND METHODS: Data from procedures on 117 eyes (91 patients) undergoing combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation for the complications of proliferative diabetic retinopathy were analyzed retrospectively. Follow-up ranged from 8 to 64 months (median = 25 months). RESULTS: Retinal tears were the most frequent intraoperative problems (19%). Limited postoperative fibrin formation occurred in 22% of eyes. Within 6 months, 7% developed glaucoma and 2% showed new anterior segment rubeosis. Overall, 10% underwent secondary surgical procedures as follows: lavage for hemorrhage (n = 3), silicone oil exchange after 7 days for focal rebleeding (n = 1), silicone oil surgery for retinal detachment after gas resorption (n = 1), and lavage for late vitreous hemorrhage (7 to 13 months) (n = 4). Half of the secondary procedures were necessitated within 3 months of the original surgery. CONCLUSIONS: Combined surgery in proliferative diabetic retinopathy is safe and effective. It should be considered when lens opacities are either present or likely to develop soon.

[Pars plana vitrectomy for pseudophakic retinal detachment]. / Primäre Pars-plana-Vitrektomie zur Behandlung der Pseudophakieamotio - eine retrospektive Studie über 129 Fälle.

BACKGROUND: Pars plana vitrectomy, usually without additional buckling procedures, is the first choice for repair of pseudophakic retinal detachment at the Lucerne Eye Hospital. PATIENTS AND METHODS: In a retrospective study we analyzed a consecutive series of 129 eyes (122 patients) treated for pseudophakic retinal detachment. All underwent a primary pars plana vitrectomy. 97 % had retrobulbar anaesthesia. SF6 was used in 93 %, Si-oil in 7 %. An additional encircling band was placed in 5 %. Mean age was 65 years (24 - 92, +/- 13). Minimal follow-up was 8 months (8 - 66, median 25). RESULTS: Mean duration of surgery was 90 minutes (50 - 140, +/- 15). Severe PVR grade C was present in 17 %. Breaks in the inferior part of the retina were found in 52 % - the localisation had no influence on the anatomical or functional outcome. A difference between preoperative and intraoperative findings was noted in 46 % (missed breaks or lattice degenerations etc.). For general medical reasons, Si-oil was not removed in 4 eyes. Complete reattachment after the first operation was achieved in overall 91 % (oil-left eyes were considered as failure); in 95 %, if the oil-left eyes were excluded from the study; in 93 %, if the eyes with encircling band were not counted; in 95 % without encircling-band and oil-left eyes; in 93 % without PVR-C cases; 95 % without encircling-band/oil-left/PVR-C eyes. Median final visual acuity was 1.0, if the macula was not detached preoperatively and 0.8, if the macula was detached. Intraocular pressure problems (> 30 mm Hg < 12 h and/or > 25 mm Hg > 36 h) were noted in 28 %. Prophylactic or therapeutic antiglaucomatous medication was applied in 58 %. 14 % showed a transient fibrin reaction in the anterior segment. Refraction and ocular motility were not influenced by the surgery. CONCLUSION: Primary vitrectomy for pseudophakic retinal detachment is safe and effective. Transient elevation of the intraocular pressure is a frequent postoperative complication.