Reticular Pseudodrusen Voids after Rhegmatogenous Retinal Detachment

We present a case of reticular pseudodrusen (RPD) regression on multimodal retinal imaging following a rhegmatogenous retinal detachment. Two mechanisms of action can be postulated. The subretinal deposits dissolve due to voluminous subretinal fluid during retinal separation from the retinal pigment epithelium and are in turn mechanically cleared during retinal re-attachment surgery. Alternatively, an RPD clearance is facilitated by enhanced phagocytic activity of macrophages and microglial cells as a response to acute retinal stress.publishedVersio

Optical coherence tomography features and risk of macular hole formation in the fellow eye

Background To investigate the risk of primary macular hole (MH) in the fellow eye, and to evaluate baseline characteristics and optical coherence tomography (OCT) features that precede MH formation in the fellow eye. Methods A retrospective review of 229 patients treated for primary MH at Stavanger University Hospital, Norway, from January 2008 through December 2018. The patients were categorised into two groups according to subsequent development of MH in the fellow eye. The OCT findings of the two groups were compared, and associated risk factors for MH formation assessed. Results Twenty cases of bilateral MH were identified. The overall bilateral disease risk was 8.8% (95% CI, 5.8–13.2%). Two patients were previously operated in the fellow eye, six patients presented with bilateral MH, and 12 patients subsequently developed MH in the fellow eye. The risk of subsequent MH development was 5.7% (95% CI, 3.3–9.8%). Although the extent of posterior vitreous detachment (PVD) tended to be more progressed in the bilateral group compared with the unilateral group, the difference was not statistically significant. In the bilateral group, 41.7% had outer retinal defects vs 6.6% in the unilateral group (p = 0.001), and 33.3% in the bilateral group had intraretinal pseudocysts vs 10.2% in the unilateral group (p = 0.036, not significant after multiple testing correction). Conclusion Outer retinal defects and intraretinal pseudocysts are associated with an increased risk of MH formation in the fellow eye, and complete PVD indicates a decreased risk of MH formation.publishedVersio

The importance of natural and anthropogenic sources for accumulation of metals and PAH in a roadside lake along RV23 : a paleolimnological survey

Langtids overvåkningsdata er som regel manglende når graden av forurensning skal avgjøres i en gitt vannforekomst. I slike tilfeller kan paleolimnologiske metoder fungere som et nyttig verktøy for å rekonstruere den historiske utviklingen i innsjøen, og gir på så måte nyttig informasjon om dens historie, naturlige tilstand og eventuell påvirkning fra det omliggende miljøet. I forbindelse med Statens Vegvesens planlagte utvidelsen av RV23 (E134), søker denne oppgaven å besvare hvilke drivkrefter som har vært viktige for de historiske tilførslene av metaller og PAH til den vegnære innsjøen Oppegårdstjern. En paleolimnologisk undersøkelse har derfor blitt benyttet for å danne et bilde av tjernets innhold av både uorganiske og organiske forbindelser gjennom en tidsperiode på cirka 150 år. Ved å kombinere dette datamaterialet med historiske regionale og lokale endringer i nedbørfeltet, kan også mulige drivkrefter til endrede konsentrasjonsforløp anslås. Tre sedimentsøyler ble tatt fra is ved det dypeste punktet i Oppegårdstjern, med påfølgende analyser på laboratoriet. Ved hjelp av radiokjemisk datering ble ulike sedimentsjikt i en av søylene tidfestet til en periode fra 1872 til 2021, mens de to resterende søylene ble videre analysert for innholdet av tretten grunnstoff (Pb, Zn, Cd, S, Cr, Ni, Cu, Co, Al, Fe, Mn, Ca, Na) og et utvalg PAH-forbindelser, kjent som 16-PAH. I tillegg ble sammensetningen av innsjøsedimentene - dry bulk density (tetthet) estimert. Konsentrasjonene i de eldste sedimentene (1872-1881) viste forholdsvis små variasjoner og ble derfor ansett som referansesedimentene i undersøkelsen. For å bestemme korrelasjon og variasjon mellom de ulike parameterne, ble det også utført en hovedkomponentanalyse, bedre kjent som principal komponent analysis (PCA), hvor sammenhengende mønstre ble påvist for flere grunnstoff. Sammenlignet med historiske endringer i tjernets nedbørfelt, viser dette studiet at endringer i konsentrasjonsforløp for både metallene og PAH kan knyttes opp mot endringer i arealbruk, klima og langtransporterte atmosfæriske avsetninger. I kombinasjon med overgangen fra permanent eng til dominans av kornproduksjon i jordbruket og de globale klimaendringene, utgjør trolig geokjemiske prosesser og transport av mineralmateriale fra nedbørfeltet viktige drivkrefter til de registrerte konsentrasjonene av Cu, Cr, Co, Ni, Al, Fe, Mn, Na og Ca i innsjøsedimentene. Innholdet av Pb, Zn, Cd og S er trolig et resultat av regionale atmosfæriske avsetninger da det naturlige bidraget fra nedbørfeltet er lite. Det samme er sannsynligvis tilfellet for de høymolekylære forbindelsene av 16-PAH.Long-term monitoring data are usually missing when the degree of pollution is to be determined in a given water body. In such cases, paleolimnological methods can serve as a useful tool for reconstructing the historical development in the lake, thus providing useful information about its history, natural state and possible effects from surrounding environment. In context with the Norwegian Public Roads Administration´s planned expansion of RV23 (E134), this task seeks to answer which driving forces that have been important for the historical supplies of metals and PAHs to the nearby lake Oppegårdstjern. A paleolimnological survey has therefore been used to form a picture of the lakes content of both inorganic and organic compounds over a period of 150 years. By combining this data material with historical regional and local changes in the catchment area, driving forces for changed concentration processes can also be estimated. Three sediment cores were taken from ice at the deepest point in Oppegårdstjern, with subsequent analyzes in the laboratory. Using radiochemical dating, the sediments were dated to a period from 1872 to 2021, and the two remaining columns were further analyzed for the content of thirteen elements (Pb, Zn, Cd, S, Cr, Ni, Cu, Co, Al, Fe, Mn, Ca, Na) and a variety of PAH compounds, known as 16-PAH. In addition, the composition of the lake sediments – dry bulk density was estimated. The concentrations in the oldest sediments (1872-1881) showed relatively small variations and were therefore considered the reference sediments in the study. In order to highlight the correlation and variation between the various parameters, a principal component analysis (PCA) was also performed, where coherent patterns were detected for several elements. Compared with historical changes in the lake´s catchment area, this study shows that changes in the concentration course of both the metals and PAH can be linked to changes in land use, climate, and long-range atmospheric deposits. In combination with the transition from permanent meadow to dominance of grain production in agriculture and global climate change, geochemical processes and transport of mineral material from the precipitation field probably constitute important driving forces for the registered concentrations of Cu, Cr, Co, Ni, Al, Fe, Mn, Na and Ca in the lake sediments. The content of Pb, Zn, Cd and S is probably a result of regional atmospheric deposits as the natural contribution from the catchment area is small. The same is probably the case for the high molecular weight compounds of 16-PAH.M-MIN

Air versus Sulfur Hexafluoride Gas Tamponade for Small and Medium-Sized Macular Holes: A Randomized Noninferiority Trial

Purpose: To investigate whether air tamponade is noninferior to sulfur hexafluoride (SF6) gas tamponade for small (≤ 250 μm) and medium-sized (> 250 μm and ≤ 400 μm) macular holes (MHs). Design: Multicenter, randomized controlled, noninferiority trial. Participants: Patients aged ≥ 18 years undergoing surgery for primary MHs of ≤ 400 μm in diameter. Methods: The patients in both groups underwent conventional pars plana vitrectomy with peeling of the internal limiting membrane. At the end of the surgery, the patients were randomized to receive either air or SF6 gas tamponades, stratified by MH size. Postoperatively, the patients followed a nonsupine positioning regimen for 3 days. Main Outcome Measures: The primary end point was the MH closure rate after a single surgery, confirmed by OCT after 2 to 8 weeks. The noninferiority margin was set at a 10–percentage-point difference in the closure rate. Results: In total, 150 patients were included (75 in each group). In the intention-to-treat (ITT) analysis, 65 of 75 patients in the air group achieved primary closure. All 75 MHs in the SF6 group closed after a single surgery. Six patients were excluded from the per-protocol (PP) analysis. In the PP analysis, 63 of 70 patients in the air group and all 74 patients in the SF6 group achieved MH closure after a single surgery, resulting in closure rates of 90% (95% confidence interval [CI], 79.9%–95.5%) and 100% (95% CI, 93.9%–100%), respectively. For the difference in closure rates, the lower bound of a 2-sided 95% CI exceeded the noninferiority margin of 10% in both ITT and PP analyses. In the subgroups of small MHs, all 20 patients in the air group and all 28 patients in the SF6 group achieved primary closure. Conclusions: This prospective randomized controlled trial proved that air tamponade is inferior to SF6 tamponade for MHs of ≤ 400 μm in diameter.publishedVersio

Associations between Serial Intravitreal Injections and Dry Eye

Purpose To investigate the effects of serial intravitreal injections (IVIs) on the ocular surface and meibomian glands (MGs) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD). Design Retrospective, controlled, observational study. Participants Patients with nAMD receiving unilateral IVIs with anti-VEGF agents. The fellow eye was used as control. Methods Tear film and ocular surface examinations were performed on a single occasion at a minimum of 4 weeks after IVI. A pre-IVI asepsis protocol with povidone-iodine (PVP-I) was applied. Main Outcome Measures Upper and lower MG loss, tear meniscus height (TMH), bulbar redness (BR) score, noninvasive tear break-up time (NIBUT), tear film osmolarity (TOsm), Schirmer test, corneal staining, fluorescein tear film break-up time (TBUT), meibomian gland expressibility (ME), and meibum quality. Results Ninety patients with a mean age of 77.5 years (standard deviation [SD], 8.4; range 54–95) were included. The median number of IVIs in treated eyes was 19.5 (range, 2–132). Mean MG loss in the upper eyelid was 19.1% (SD, 11.3) in treated eyes and 25.5% (SD, 14.6) in untreated fellow eyes (P = 0.001). For the lower eyelid, median MG loss was 17.4% (interquartile range [IQR], 9.4–29.9) in treated eyes and 24.5% (IQR, 14.2–35.2) in fellow eyes (P < 0.001). Mean BR was 1.32 (SD, 0.46) in treated eyes versus 1.44 (SD, 0.45) in fellow eyes (P = 0.017). Median TMH was 0.36 mm (IQR, 0.28–0.52) in treated eyes and 0.32 mm (IQR, 0.24–0.49) in fellow eyes (P = 0.02). There were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, ME, or meibum quality. Conclusions Repeated IVIs with anti-VEGF with preoperative PVP-I application was associated with reduced MG loss, increased tear volume, and reduced signs of inflammation compared with fellow nontreated eyes in patients with nAMD. This regimen may thus have a beneficial effect on the ocular surface.publishedVersio

The Treatment of Hallucinations in Schizophrenia Spectrum Disorders

This article reviews the treatment of hallucinations in schizophrenia. The first treatment option for hallucinations in schizophrenia is antipsychotic medication, which can induce a rapid decrease in severity. Only 8% of first-episode patients still experience mild to moderate hallucinations after continuing medication for 1 year. Olanzapine, amisulpride, ziprasidone, and quetiapine are equally effective against hallucinations, but haloperidol may be slightly inferior. If the drug of first choice provides inadequate improvement, it is probably best to switch medication after 2-4 weeks of treatment. Clozapine is the drug of choice for patients who are resistant to 2 antipsychotic agents. Blood levels should be above 350-450 mu g/ml for maximal effect. For relapse prevention, medication should be continued in the same dose. Depot medication should be considered for all patients because nonadherence is high. Cognitive-behavioral therapy (CBT) can be applied as an augmentation to antipsychotic medication. The success of CBT depends on the reduction of catastrophic appraisals, thereby reducing the concurrent anxiety and distress. CBT aims at reducing the emotional distress associated with auditory hallucinations and develops new coping strategies. Transcranial magnetic stimulation (TMS) is capable of reducing the frequency and severity of auditory hallucinations. Several meta-analyses found significantly better symptom reduction for low-frequency repetitive TMS as compared with placebo. Consequently, TMS currently has the status of a potentially useful treatment method for auditory hallucinations, but only in combination with state of the art antipsychotic treatment. Electroconvulsive therapy (ECT) is considered a last resort for treatment-resistant psychosis. Although several studies showed clinical improvement, a specific reduction in hallucination severity has never been demonstrated

Improved Outcomes with Heavy Silicone Oil in Complex Primary Retinal Detachment: A Large Multicenter Matched Cohort Study

\ua9 2023 American Academy of OphthalmologyPurpose: To establish whether Densiron 68, a heavier-than-water endotamponade agent, is an effective alternative to conventional light silicone oil in primary rhegmatogenous retinal detachment (RD) surgery for eyes with inferior breaks in the detached retina and severe proliferative vitreoretinopathy (PVR). Design: Cohort study of routinely collected data from the European Society of Retina Specialists and British and Eire Association of Vitreoretinal Surgeons vitreoretinal database between 2015 and 2022. Participants: All consecutive eyes that underwent primary rhegmatogenous RD surgery using Densiron 68 or light silicone oil as an internal tamponade agent. Methods: To minimize confounding bias, we undertook 2:1 nearest-neighbor matching on inferior breaks, large inferior rhegmatogenous RDs, PVR, and, for visual analyses, baseline visual acuity (VA) between treatment groups. We fit regression models including prognostically relevant covariates, treatment–covariate interactions, and matching weights. We used g-computation with cluster-robust methods to estimate marginal effects. For nonlinear models, we calculated confidence intervals (CIs) using bias-corrected cluster bootstrapping with 9999 replications. Main Outcome Measures: Presence of a fully attached retina and VA at least 2 months after oil removal. Results: Of 1061 eyes enrolled, 426 and 239 were included in our matched samples for anatomic and visual outcome analyses, respectively. The primary success rate was higher in the Densiron 68 group (113 of 142; 80%) compared with the light silicone oil group (180 of 284; 63%), with an adjusted odds ratio of 1.90 (95% CI, 1.63–2.23, P &lt; 0.001). We also observed a significant improvement favoring Densiron 68 of –0.26 logarithm of the minimum angle of resolution (logMAR) in postoperative VA between the 2 groups (95% CI, –0.43 to –0.10, P = 0.002). The anatomic benefit of using Densiron 68 in eyes with inferior retinal breaks and large detachments was more pronounced among eyes with PVR grade C. We found no evidence of visual effect moderation by anatomic outcome or foveal attachment. Conclusions: Densiron achieved higher anatomic success rates and improved visual outcomes compared with conventional light silicone oil in eyes with inferior retinal pathology and severe PVR. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

α-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease

Currently, there are no reported genetic predictors of motor symptom progression in Parkinson’s disease (PD). In familial PD, disease severity is associated with higher α-synuclein (SNCA) expression levels, and in postmortem studies expression varies with SNCA genetic variants. Furthermore, SNCA is a well-known risk factor for PD occurrence. We recruited Parkinson’s patients from the communities of three central California counties to investigate the influence of SNCA genetic variants on motor symptom progression in idiopathic PD. We repeatedly assessed this cohort of patients over an average of 5.1 years for motor symptom changes employing the Unified Parkinson’s Disease Rating Scale (UPDRS). Of 363 population-based incident PD cases diagnosed less than 3 years from baseline assessment, 242 cases were successfully re-contacted and 233 were re-examined at least once. Of subjects lost to follow-up, 69% were due to death. Adjusting for covariates, risk of faster decline of motor function as measured by annual increase in motor UPDRS exam score was increased 4-fold in carriers of the REP1 263bp promoter variant (OR 4.03, 95%CI:1.57–10.4). Our data also suggest a contribution to increased risk by the G-allele for rs356165 (OR 1.66; 95%CI:0.96–2.88), and we observed a strong trend across categories when both genetic variants were considered (p for trend  = 0.002). Our population-based study has demonstrated that SNCA variants are strong predictors of faster motor decline in idiopathic PD. SNCA may be a promising target for therapies and may help identify patients who will benefit most from early interventions. This is the first study to link SNCA to motor symptom decline in a longitudinal progression study

Biomarker candidates of neurodegeneration in Parkinson’s disease for the evaluation of disease-modifying therapeutics

Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson’s disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies