Showing papers in "Graefes Archive for Clinical and Experimental Ophthalmology in 2022"

A new insight into pachychoroid diseases: Remodeling of choroidal vasculature

Abstract: Pachychoroid spectrum diseases are regarded as being different manifestations of a common pathogenic process. We suggest that pachychoroid diseases are consequences of chronic vortex vein stasis.We describe how we came to this conclusion based on our own recent reports as well as a search of the related literature.Central serous chorioretinopathy (CSC) is the first stage of pachychoroid spectrum diseases. CSC is caused by congestion of choroidal veins, which are branches of the vortex veins. The venous outflow tract of the choroid is divided into four quadrants, based on horizontal and vertical watershed zones, with one or two vortex veins in each quadrant being independently responsible for venous outflow. In acute CSC, vortex vein stasis frequently causes asymmetric dilatation of the vortex veins in the horizontal watershed. The area of geographic filling delay in the choriocapillaris coincides with the area of this asymmetrically dilated vortex veins. With chronic stasis of the vortex veins, venous anastomosis occurs in the watershed zone as a means of compensating for the stasis, and the choriocapillaris becomes occluded in the area of filling delay. The anastomotic vessels dilate, becoming often hyperpermeable, and are then recognizable as pachyvessels. With the development of choriocapillaris ischemia, choroidal neovascularization (CNV) occurs at the site of pachyvessels. This is termed pachychoroid neovasculopathy (PNV). Polypoidal choroidal vasculopathy is regarded as a variant of PNV.Intervortex venous anastomosis is among the key factors underlying the development of pachychoroid diseases. Remodeling of the venous drainage route though the anastomosis across the watershed zones is apparently a common response to chronic vortex vein stasis.

Role of Curcumin in Retinal Diseases—A review

Abstract: To review the role of curcumin in retinal diseases, COVID era, modification of the molecule to improve bioavailability and its future scope. PubMed and MEDLINE searches were pertaining to curcumin, properties of curcumin, curcumin in retinal diseases, curcumin in diabetic retinopathy, curcumin in age-related macular degeneration, curcumin in retinal and choroidal diseases, curcumin in retinitis pigmentosa, curcumin in retinal ischemia reperfusion injury, curcumin in proliferative vitreoretinopathy and curcumin in current COVID era. In experimental models, curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteins and cellular inflammatory genes and upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa, curcumin has been shown to delay structural defects of P23H gene in P23H-rhodopsin transgenic rats. In proliferative vitreoretinopathy, curcumin inhibited the action of EGF in a dose- and time-dependent manner. In retinal ischemia reperfusion injury, curcumin downregulates IL-17, IL-23, NFKB, STAT-3, MCP-1 and JNK. In retinoblastoma, curcumin inhibits proliferation, migration and apoptosis of RBY79 and SO-RB50. Curcumin has already proven its efficacy in inhibiting viral replication, coagulation and cytokine storm in COVID era. Curcumin is an easily available spice used traditionally in Indian cooking. The benefits of curcumin are manifold, and large randomized controlled trials are required to study its effects not only in treating retinal diseases in humans but in their prevention too.

Clinically applicable deep learning-based decision aids for treatment of neovascular AMD

Abstract: Anti-vascular endothelial growth factor (Anti-VEGF) therapy is currently seen as the standard for treatment of neovascular AMD (nAMD). However, while treatments are highly effective, decisions for initial treatment and retreatment are often challenging for non-retina specialists. The purpose of this study is to develop convolutional neural networks (CNN) that can differentiate treatment indicated presentations of nAMD for referral to treatment centre based solely on SD-OCT. This provides the basis for developing an applicable medical decision support system subsequently.SD-OCT volumes of a consecutive real-life cohort of 1503 nAMD patients were analysed and two experiments were carried out. To differentiate between no treatment class vs. initial treatment nAMD class and stabilised nAMD vs. active nAMD, two novel CNNs, based on SD-OCT volume scans, were developed and tested for robustness and performance. In a step towards explainable artificial intelligence (AI), saliency maps of the SD-OCT volume scans of 24 initial indication decisions with a predicted probability of > 97.5% were analysed (score 0-2 in respect to staining intensity). An AI benchmark against retina specialists was performed.At the first experiment, the area under curve (AUC) of the receiver-operating characteristic (ROC) for the differentiation of patients for the initial analysis was 0.927 (standard deviation (SD): 0.018), for the second experiment (retreatment analysis) 0.865 (SD: 0.027). The results were robust to downsampling (¼ of the original resolution) and cross-validation (tenfold). In addition, there was a high correlation between the AI analysis and expert opinion in a sample of 102 cases for differentiation of patients needing treatment (κ = 0.824). On saliency maps, the relevant structures for individual initial indication decisions were the retina/vitreous interface, subretinal space, intraretinal cysts, subretinal pigment epithelium space, and the choroid.The developed AI algorithms can define and differentiate presentations of AMD, which should be referred for treatment or retreatment with anti-VEGF therapy. This may support non-retina specialists to interpret SD-OCT on expert opinion level. The individual decision of the algorithm can be supervised by saliency maps.

Intravitreal aflibercept for diabetic macular edema in real-world clinical practice in Japan: 24-month outcomes

Abstract: To report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan.In this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency.In total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 μm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 μm (n = 140) at 24 months.Routine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice.ClinicalTrials.gov: NCT02425501.

Incidence, prevalence, and outcome of moderate to severe neurotrophic keratopathy in a German tertiary referral center from 2013 to 2017

Abstract: Neurotrophic keratopathy (NK) is an orphan disease, with an estimated prevalence of 1-5/10,000. No data regarding the incidence exists. The primary aim was to evaluate incidence and prevalence of NK at a tertiary referral center in Germany, and the secondary aim was to analyze demographic parameters, etiology, and clinical features and therapeutic outcomes.All patients treated for NK with serum eye drops (SED), amnionic membrane transplantation (AMT), or penetrating keratoplasty (PK) in 2013-2017 were identified. Age, sex, etiology of NK, visual acuity, disease stage, treatment, and visual acuity were analyzed. Incidence and prevalence of NK in our hospital and the overall population of the city were calculated.In 63 eyes of 60 patients (56.7% male; 68 ± 16 years), the most common underlying diseases were herpetic infections (23.8%), neurological causes (19%), and diabetes mellitus (14.3%). The annual incidence of NK in our tertiary referral center ranges between 5/10,000 and 3/10,000, the prevalence between 9/10,00 and 22/10,000. In all patients treated with corneal ulcers, the prevalence was up to 27% (2706/10,000). The incidence in the overall population is estimated at 0.1-0.3/10,000, the prevalence at 0.2-0.5/10,000 to 0.5/10,000.Based on our assessment, the prevalence of NK in the overall population is lower than estimated before. However, in patients with corneal ulcers, the percentage of NK is comparably high. The disease may still be underdiagnosed due to the variety of underlying disorders and unknown comorbidities. Thus, in cases of therapy-refractive superficial keratopathy or ulcerations, NK should be considered more frequently.

Rhegmatogenous retinal detachment repair—does age, sex, and lens status make a difference?

Abstract: To analyze the correlation between lens status, age, and sex in the epidemiology and success rates of rhegmatogenous retinal detachment (RRD) surgery.The files of all consecutive patients undergoing vitreoretinal surgery for uncomplicated RRD between Jan 2005 und Dec 2020 were retrospectively reviewed. Successful outcome was defined as no retinal redetachment occurring within 3 months after surgery.5502 eyes with uncomplicated primary RRD were included. Mean age of the patients was 61.1 years (± 13.6 SD). In the age group over 40 years, a male predominance was found. The percentage of pseudophakic RRD increased from 25 to 40% during the 15 years observation period. In the age group 50 to 69 years, patients with pseudophakic detachments were male in 786 out of 1079 cases (72.9%). In the same age group, 1285 of 2110 (60.9%) patients with phakic RRD were male. Overall, primary success rate after one procedure was 91.2% (5018 of 5502). In the phakic eyes, the primary success rate was higher in those eyes that underwent combined phacovitrectomy (93.0%), compared to those without simultaneous cataract surgery (88.7%; p = 0.002).The ratio of male and female patients with RRD varies between age groups. The proportion of pseudophakic RRD has increased within 15 years. The male predominance in RRD is stronger in pseudophakic than in phakic eyes. In phakic eyes with RRD, a combined phacovitrectomy yielded better anatomical results.

Acute intraocular toxicity caused by perfluorocarbon liquids: safety control systems of medical devices

Abstract: Acute retinal toxicity has been demonstrated to be associated with the intraoperative use of perfluorocarbon liquids (PFCLs), especially perfluorooctane (PFO). Recently, several cases of PFO-associated blindness have been reported in Spain, Holland, France, Italy, the Middle East, and South America. As a result, a new ISO guideline (ISO 16672:2020) was drafted, discussed, approved, and released in 2019. This recent ISO16672:2020 guideline recommends performing direct cytotoxicity tests as an option along with chemical analysis to measure PFCL quality (purity and safety). In this review paper, it has been emphasized why an appropriate biological test, specifically direct exposure of PFCL to live cells, for measuring cytotoxicity must be performed with each PFCL batch along with chemical analysis. The paper intends to compile all available information to discuss possible approaches for avoiding adverse clinical cases in future.

Visual and optical quality of enhanced intermediate monofocal versus standard monofocal intraocular lens

Abstract: Intraocular lens designs are constantly evolving, trying to obtain more spectacle independence after cataract surgery. This advantage can be linked to some disadvantages, such as optical quality decrease. For that reason, it is important to assess, not only the amount of vision provided but also the quality of vision once they are implanted. The purpose of the present work was to compare the visual performance between two monofocal intraocular models: a standard model and a monofocal with enhanced intermediate vision lens.Prospective, randomized, comparative study. Sixty adult subjects scheduled to undergo bilateral cataract surgery and IOL implantation were randomized to receive one of the two IOLs in both eyes at Miranza IOA, Madrid, Spain (group A: monofocal with enhanced intermediate vision lens and group B: standard monofocal lens). Monocular outcomes (right eyes) determined 1 and 3 months postoperatively were photopic corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), perceived halo, corrected intermediate-distance contrast sensitivity, and higher-order aberrations. The impact of the new IOL in the postoperative management with autorefraction devices was also evaluated.No differences were found in CDVA between the two groups. Significant differences were detected between the two lenses evaluated in both total HOA (p = 0.028) and internal HOA (p = 0.037). Contrast sensitivity and halometry results obtained at 1 month were similar across the two IOL groups.In patients undergoing cataract surgery, monofocal with enhanced intermediate vision IOL offered similar distance performance and contrast sensitivity along with perceived HOA and halos compared with the standard monofocal IOLs tested.

Morphological characterization and clinical effects of stromal alterations after intracorneal ring segment implantation in keratoconus

Abstract: To analyze the histological and (ultra)structural stromal tissue changes after femtosecond (Fs) laser-assisted intracorneal ring segment (ICRS) implantation and their refractive and topographic effects in patients with keratoconus.This monocentric retrospective case series included 15 consecutive patients with clinical peri-segmental lamellar channel deposits after treatment with Fs-ICRS implantation for keratoconus. The stromal changes were investigated using in vivo confocal microscopy. Two patients underwent a penetrating keratoplasty after the Fs-ICRS implantation; the explanted corneas were processed for histopathology and transmission electron microscopy (TEM). Refractive and topographic effects were investigated comparing the uncorrected (UDVA) and corrected (CDVA) distance visual acuity, spherical equivalent (SE), flat (K1), steep (K2), and steepest (Kmax) keratometry before and after detection of lamellar channel deposits.In vivo confocal microscopy revealed diffuse linear and focal granular hyperreflective structures. Histologically, there was mild proliferation of fibroblasts and fibrosis. TEM demonstrated focal accumulations of degenerated keratocytes with cytoplasmic lipid inclusions. There were no significant changes for UDVA (Δ = 0.0 ± 0.2 logMAR; p = 0.67), CDVA (Δ = 0.0 ± 0.1 logMAR; p = 0.32), SE (Δ 0.1 ± 0.9 D; p = 0.22), K1 (Δ = 0.3 ± 1.0 D; p = 0.28), K2 (Δ = 0.1 ± 0.9 D; p = 0.51), and Kmax (Δ = 0.3 ± 1.5 D; p = 0.17).Two types of structural stromal changes were identified: (1) diffuse peri-segmental fibrosis and (2) lamellar channel deposits. These structural changes showed no evidence of a relevant refractive or topographic effect.

Effects of delay in anti-vascular endothelial growth factor intravitreal injections for neovascular age-related macular degeneration

Abstract: To assess the impact of COVID-19-related delay in intravitreal injection timing on macular structure and visual acuity (VA) among patients treated for neovascular age-related macular degeneration (nvAMD).We reviewed demographic and clinical data and macular ocular computerized tomographic images of 34 patients (48 eyes, group A) who did not follow their injection schedule during the first wave of COVID-19 and compared them to 46 patients (71 eyes, group B) who did. Functional worsening was defined as a loss of at least 0.1 in decimal VA. Anatomic worsening was defined as new or increased subretinal/intraretinal fluids or new hemorrhage.The planned mean ± standard deviation intervals between the intravitreal injections were 5.7 ± 2.7 weeks for group A and 5.5 ± 2.4 weeks for group B (P = 0.60). The actual intervals were 13.6 ± 6.8 (7.9 ± 5.2 weeks' delay) and 5.3 ± 2.4 weeks (no delay), respectively (P < 0.001). The best corrected visual acuity worsened in 23 group A eyes (47.9%) and in 6 group B eyes (8.5%) (odds ratio [OR] 9.97, P < 0.001). Anatomic features indicative of nvAMD worsening were detected in 31 group A eyes (64.6%) and in 16 group B eyes (22.5%) (OR 5.73, P < 0.001). A new macular hemorrhage was observed in 4 group A eyes (8.3%) and in no group B eyes (P = 0.09).Delay in timely retinal care during the COVID-19 restrictions period resulted in short-term negative outcomes, including macular bleeding, in nvAMD patients.

A comparison of long-term results after Baerveldt 250 implantation in advanced uveitic vs. other forms of glaucoma

Abstract: Abstract Introduction Uveitic glaucoma remains challenging despite medical and surgical advancements and can potentially lead to blindness if left uncontrolled. Conservative alternatives as well as microinvasive surgeries can postpone the necessity of a highly invasive intervention. However, such procedures are still necessary to treat some refractive glaucoma cases. Since previous studies have reported excellent results following the primary implantation of glaucoma drainage devices, it was our study’s aim to evaluate long-term results following a Baerveldt 250 implantation in highly complex and surgically burdened uveitic glaucoma eyes (UG) and compare these to a similar population suffering from other forms of glaucoma (OFG). Material and methods We performed a retrospective analysis of all eyes (UG vs. OFG) following a Baerveldt 250 implant between 2013 and 2019. Efficacy parameters as well as post-operative complication data were extracted from our electronic data system for statistical analysis. Results A total of 62 eyes were included in our study (24 UG and 38 OFG). UG baseline mean IOP was 35.04 mmHg (± 11.85 mmHg) with 3.08 (± 1.13) topical agents, and OFG was 32.63 mmHg (± 7.74 mmHg) with 2.68 (± 1.28) topical agents. A majority of eyes also required systemic acetazolamide (UG: 79% OFG: 87%) and had undergone at least one glaucoma-related operation prior to the Baerveldt 250 implant ((UG: 1.21 (± 0.66)), OFG: 1.74 (± 1.33)). At the median follow-up period (UG 592, OFG 764 days), 52.5%/32.5% of UG/OFG cases showed qualified success (IOP below 21 mmHg with either topical or/and systemic medication), 15%/30% no longer required topical medication, and 47.5% /47.5% were free of acetazolamide systemically. Moreover, 75%/72.5% of eyes experienced no further pressure-related surgical event. Although sight-threatening complications such as corneal and macular edema were reported in both groups, most either maintained or improved their visual acuity at the last follow-up (58.33%/57.89%). Conclusion The Baerveldt 250 implant is shown to be both effective and safe for advanced glaucoma cases in uveitis and other forms. No further glaucoma-related surgery is required in the majority of eyes in either group within a follow-up period of almost 2 years. Despite sight-threatening complications such as macular and corneal edema, visual acuity can be either maintained or improved in most eyes.

Impact of the COVID-19 pandemic’s first wave on the care and treatment situation of intravitreal injections in a German metropolitan region

Abstract: This study aims to evaluate the impact of the first coronavirus 2019 (COVID-19) wave in 2020 on patients scheduled for intravitreal injections (IVI) in a German metropolitan region.We performed a multicentre prospective survey and retrospective analysis of the records of patients treated with intravitreal injections during the 20-week period from March to July 2020 in all four hospital eye departments in the city of Hamburg using a questionnaire (on treatment adherence, SarsCoV2-related personal, familial and social data) and treatment data.A total of 1038 patients (2472 IVI, 1231 eyes) and 818 questionnaires were evaluated. Longer duration of therapy, lower visual acuity (VA) of the treated and higher VA of the fellow untreated eye was were associated with a higher probability of visit cancellation. Every additional year of life posed a 2.6% lower risk of noncompliance. A COVID-19 infection in the family environment displayed a 5.5-fold chance of visit cancellation. Patients treated for neovascular age-related macular degeneration (nAMD) had a 36% reduced risk of visit cancellation compared to patients with diabetic macular oedema (DME).A long preceding treatment period, low VA of the treated eye, high VA of the untreated eye, COVID-19 in the family and DME were identified as risk factors for IVI visit cancellations during the COVID-19 pandemic. Compliance to treatment might be improved in the future by taking these risk factors into account when scheduling patients for IVI during the exceptional circumstances of a pandemic.

Surgery-related characteristics, efficacy, safety and surgical team satisfaction of three-dimensional heads-up system versus traditional microscopic equipment for various vitreoretinal diseases

Abstract: To compare the three-dimensional (3D) heads-up surgery with the traditional microscopic (TM) surgery for various vitreoretinal diseases.A medical record review of patients that underwent 3D heads-up or TM vitreoretinal surgeries was performed from May 2020 to October 2021 in this retrospective case-control study. Main outcome measures included surgery-related characteristics, efficacy, safety, and satisfaction feedback from the surgical team.A total of 220 (47.6%) and 242 (52.4%) eyes were included in the 3D and TM groups, respectively. The 3D heads-up system significantly benefits delicate surgical steps, like the epiretinal membrane (ERM) peeling for ERM and internal limiting membrane peeling for idiopathic macular holes (P < 0.05). The 3D heads-up system could facilitate a significantly better visual outcome for pathologic myopic foveoschisis (P = 0.049), while no difference by TM surgery (P = 0.45). For the satisfaction feedback, the 3D heads-up system was rated significantly higher in most subscales and the overall score (P < 0.05). The surgeons' ratings on operating accuracy and the first assistants' rating on operating accuracy and operation cooperation were significantly higher in the TM group than in the 3D group (P < 0.05). Besides that, the 3D heads-up surgery was comparable with TM surgery in the surgery-related characteristics, choice of tamponades, postoperative VA, primary anatomic success, and perioperative complications (P > 0.05).The efficacy and safety of the 3D heads-up surgery were generally comparable to the TM surgery. The 3D heads-up system could significantly benefit delicate surgical steps and achieve better surgical team satisfaction.

Automated foveal location detection on spectral-domain optical coherence tomography in geographic atrophy patients

Abstract: Abstract Purpose To develop a fully automated algorithm for accurate detection of fovea location in atrophic age-related macular degeneration (AMD), based on spectral-domain optical coherence tomography (SD-OCT) scans. Methods Image processing was conducted on a cohort of patients affected by geographic atrophy (GA). SD-OCT images (cube volume) from 55 eyes (51 patients) were extracted and processed with a layer segmentation algorithm to segment Ganglion Cell Layer (GCL) and Inner Plexiform Layer (IPL). Their en face thickness projection was convolved with a 2D Gaussian filter to find the global maximum, which corresponded to the detected fovea. The detection accuracy was evaluated by computing the distance between manual annotation and predicted location. Results The mean total location error was 0.101±0.145mm; the mean error in horizontal and vertical en face axes was 0.064±0.140mm and 0.063±0.060mm, respectively. The mean error for foveal and extrafoveal retinal pigment epithelium and outer retinal atrophy (RORA) was 0.096±0.070mm and 0.107±0.212mm, respectively. Our method obtained a significantly smaller error than the fovea localization algorithm inbuilt in the OCT device (0.313±0.283mm, p <.001) or a method based on the thinnest central retinal thickness (0.843±1.221, p <.001). Significant outliers are depicted with the reliability score of the method. Conclusion Despite retinal anatomical alterations related to GA, the presented algorithm was able to detect the foveal location on SD-OCT cubes with high reliability. Such an algorithm could be useful for studying structural-functional correlations in atrophic AMD and could have further applications in different retinal pathologies.

Anatomical and functional outcomes of pneumatic vitreolysis for treatment of vitreomacular traction with and without macular holes

Abstract: Abstract Purpose To evaluate the outcome of pneumatic vitreolysis (PVL) for vitreomacular traction (VMT) with or without full thickness macular hole (MH) < 400 µm. Methods Forty-seven eyes of 47 patients were included who had undergone PVL for VMT with or without MH. Main outcome measures were release of VMT, MH closure, best-corrected visual acuity (BCVA) and adverse events. Results Thirty-three patients had isolated VMT and 14 patients VMT with a MH. Four weeks after PVL, the overall VMT release rate was 35/47 (74.5%): 25/37 (67.6%) in phakic and 10/10 (100%) in pseudophakic eyes ( p = 0.03). Four of 14 MH (28.6%) were closed. Twenty-two of 47 (46.8%) eyes required a subsequent PPV: 12/33 (36.4%) in the VMT only group and 10/14 (71.4%) in the VMT with MH group. Mean BCVA improved from 0.48 (± 0.24) to 0.34 (± 0.23) logMAR at 6 months in patients with VMT alone ( p < 0.001), and from 0.57 (± 0.27) to 0.41 (± 0.28) logMAR in patients with VMT and MH ( p = 0.008). Adverse events included new formation of a large MH in 4/33 (12.1%) eyes, failure of MH closure in 10/14 (71.4%) eyes, progression of mean minimum linear diameter (MLD) MH size from baseline 139 (± 67) to 396 (± 130) µm ( p < 0.001) and development of a retinal detachment in 4/47 (8.5%) eyes. Conclusion While PVL leads to a high VMT release rate particularly in pseudophakic eyes, it is associated with a relatively high incidence of MH formation, MH size progression and retinal detachment.