MD Research News – Issue 429 – 18 July 2019
Drug treatment
Expert Opin Pharmacother. 2019 Jul 12:1-13.
Innovative therapies for neovascular age-related macular degeneration.
Al-Khersan H, Hussain RM, Ciulla TA, Dugel PU.
Abstract: Introduction: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include long-acting agents, combination strategies, topical agents, sustained-release, and genetic therapies. Areas covered: The authors provide a comprehensive review of investigational therapies for nAMD, focusing on therapies currently in clinical trial. Expert opinion: Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept - a fusion protein of the VEGF receptor domains, KSI-301 - an anti-VEGF antibody biopolymer conjugate, and OPT-302 - an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305. Similarly, genetic therapies, including RGX-314 and ADVM-022, aim to provide sustained anti-VEGF expression from the retina.
PMID: 31298960 DOI: 10.1080/14656566.2019.1636031
Graefes Arch Clin Exp Ophthalmol. 2019 Jul 9.
Treatment compliance and adherence among patients with diabetic retinopathy and age-related macular degeneration treated by anti-vascular endothelial growth factor under universal health coverage.
Angermann R, Rauchegger T, Nowosielski Y, Casazza M, Bilgeri A, Ulmer H, Zehetner C.
Purpose: To analyze and compare loss to follow-up (LTFU) rates between patients with diabetic retinopathy (DR) and those with neovascular age-related macular degeneration (nAMD) in patients, receiving treatment with anti-vascular endothelial growth factor (VEGF), under universal health coverage.
Methods: We retrospectively analyzed the relevant data of 1264 patients receiving anti-VEGF therapy, in this cohort study. The observation period ranged from September 01, 2015 to December 31, 2018. Intervals between each procedure and the subsequent follow-up examination were measured. Demographic data, visual acuity (VA), the type of transport for treatment access, and distance between the residence and clinic were evaluated as risk factors for LTFU.
Results: We collected data for 841 patients with nAMD (age, 81.0 (± 8.1 years)) and 423 patients with DR (age, 67.7 (± 12.1 years)). The rate of LTFU, for at least 6 months, was 28.8% and 2.9% for patients with DR and nAMD, respectively (p < 0.001). In the DR group, 18.9% patients were lost to follow-up exceeding > 12 months. Multivariate regression analysis showed that advanced age, lack of mobility, and need for assisted transport, poor final VA despite treatment, and decrease in vision during the observational period were independent risk factors for LTFU exceeding 12 months (p < 0.05).
Conclusions: We found a high long-term LTFU rate for patients with DR, despite treatment under universal health coverage. Considering the risk of disease progression, particularly in patients with chronic DR, strategies for better compliance and adherence to therapy should be considered for optimized patient care.
PMID: 31286206 DOI: 10.1007/s00417-019-04414-y
Ophthalmol Retina. 2019 May 17. pii: S2468-6530(19)30015-6.
Outcomes of suspending VEGF inhibitors for neovascular age-related macular degeneration when lesions have been inactive for 3 months.
Nguyen V, Vaze A, Fraser-Bell S, Arnold J, Essex RW, Barthelmes D, Gillies MC; Fight Retinal Blindness! Study Group.
Purpose: Currently, little evidence supports the safety of suspending vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration (nAMD). We assessed the outcomes of eyes in which this seems to have been attempted.
Design: Observational study from a prospectively designed database.
Participants: Eyes enrolled in the Fight Retinal Blindness! registry of nAMD treatment outcomes were considered to have suspended treatment if they had a 3-month or longer documented period of inactivity of the choroidal neovascular lesion with no further treatments unless the lesion re-activated.
Methods: Time and proportion to re-activation of the lesion were analyzed using Kaplan-Meier survival curves. Visual outcomes after treatment suspension were assessed with paired t tests.
Main Outcome Measures: The proportion of eyes resuming treatment because of lesion re-activation, change in visual acuity (VA) at time of re-activation, and recovery of vision 12 months later.
Results: We identified 434 eyes in which treatment was suspended and that were tracked for at least 12 months thereafter. The estimated percentage of eyes re-activating in the first year after treatment suspension was 41%, increasing to 79% by the fifth year. The median time to re-activation was 504 days. The 275 eyes whose lesion was observed to re-activate lost a mean of 4.2 letters (95% confidence interval [CI], -5.6 to -2.8 letters; P < 0.001) from the last injection to the time of re-activation; 206 eyes resumed treatment for at least 12 months after re-activation and recovered a mean of +1.2 letters (95% CI, -0.4 to 2.7 letters; P = 0.133), resulting in a net loss of 3.3 letters (95% CI, 2.3-5.1 letters; P < 0.001) compared with VA at treatment suspension. Lower VA at the time of suspension and longer duration of treatment were associated with reduced risk of re-activation. Median time to re-activation was substantially greater when eyes had been treated for at least 3 years.
Conclusions: Fewer than half of the eyes in which treatment was suspended re-activated in the first year, but most re-activated by the fifth year. Caution should be exercised to avoid suspending treatment prematurely. Further research is warranted to identify the eyes in which treatment may be suspended safely.
PMID: 31281103 DOI: 10.1016/j.oret.2019.05.013
Ophthalmol Retina. 2019 Jul;3(7):561-566.
Aflibercept for radiation maculopathy study: A prospective, randomized clinical study.
Murray TG, Latiff A, Villegas VM, Gold AS.
Purpose: To evaluate 2 treatment approaches to intravitreal vascular endothelial growth factor antagonist therapy in radiation maculopathy comparing aflibercept delivered by either a 6-week treatment interval or treat-and-adjust interval.
Design: Randomized, prospective clinical trial.
Methods: Forty consecutive patients were enrolled in an institutional review board-approved clinical trial and randomized to aflibercept treatment via 1 of 2 regimens: (1) fixed, every-6-weeks treatment or (2) variable, treat-and-adjust treatment centered around 6 weeks. All patients had a diagnosis of treated uveal melanoma with documented tumor control. All patients showed visually compromising radiation maculopathy confirmed by a decline in best-corrected visual acuity (BCVA) and spectral-domain (SD) OCT documentation of radiation maculopathy.
Main Outcome Measures: Best-corrected visual acuity and SD OCT central retinal thickness at 1 year.
Results: Thirty-nine of 40 patients completed the trial (97.5%) with 1 year of follow-up. Baseline study entry BCVA was 20/63 and was maintained at 20/62 at study conclusion at 60 weeks (1 year). At baseline, SD OCT mean central retinal thickness was 432 μm and improved to 294 μm at 60 weeks (P < 0.02). At the study conclusion, 42.5% of eyes (17/40) showed better than 20/50 BCVA, and only 5% of eyes (2/40) showed a BCVA worse than 20/200. In the every-6-weeks interval treatment arm, patients received 9 injections, whereas in the treat-and-adjust study arm, patients received 8.4 injections (P = 0.88, not significant). One patient experienced an inflammatory response after aflibercept injection, but this did not occur again for this patient, nor for any other study injections (1/400 injections [0.0025%]). No patients demonstrated endophthalmitis or metastatic disease or died during the study window.
Conclusions: Aflibercept seems to limit vision loss associated with radiation maculopathy. In this randomized, prospective clinical study, no difference was found between a fixed 6-week treatment interval and a variable treat-and-adjust interval because virtually all patients required treatment every 6 weeks and were not able to extend. Remarkably, almost half of all treated patients maintained BCVA of 20/50 or better throughout 1 year of treatment. Aflibercept is effective in treating radiation maculopathy, but requires an ongoing treatment approach.
PMID: 31277797 DOI: 10.1016/j.oret.2019.02.009
Acta Ophthalmol. 2019 Jul 3.
Task shifting of intraocular injections from physicians to nurses: a randomized single-masked noninferiority study.
Bolme S, Morken TS, Follestad T, Sørensen TL, Austeng D.
Purpose: To test if task shifting of intraocular injections to nurses in a real-world setting can result in similar visual function outcome with equal safety profile.
Method: All patients with either age-related macular degeneration, retinal vein occlusion or diabetic macular oedema remitted to intraocular injections at a tertiary ophthalmology department in Norway between March 2015 and May 2017, were asked to participate. The participants were randomized to either nurse- or physician-administered intraocular injections of anti-vascular endothelial growth factor. The primary outcome measure was change in best-corrected visual acuity from baseline to 1-year follow-up. The mean difference in the primary outcome between the groups was analysed by a noninferiority test with a margin of three letters in disfavour of the nurse group. Adverse events were recorded.
Results: Three hundred and forty-two patients entered the study. Two hundred and fifty-nine completed the 1-year follow-up and were included in the study sample for the analysis of the primary outcome. Nurse-administered intraocular injections were noninferior to physician-administered injections with 0.7 and 1.6 letters gained, respectively (95% CI of the mean difference, -2.9 to 1.0; p = 0.019, one-sided t-test). Two thousand and seventy-seven injections and three ocular adverse events were recorded.
Conclusion: Task shifting of intraocular injections to nurses can be performed without increased risk to visual function. Such a task shift can alleviate the burden of performing intraocular injections in ophthalmology departments. To our knowledge, this is the first RCT on task shifting of a surgical procedure from physicians to nurses in a high-income country.
PMID: 31267688 DOI: 10.1111/aos.14184
Clin Exp Ophthalmol. 2019 Jul 2.
Effects of VEGF inhibitors on human retinal pigment epithelium under high glucose and hypoxia.
Bahrami B, Shen W, Zhu L, Zhang T, Chang A, Gillies M.
Background: Retinal pigment epithelium (RPE) is known to secrete factors important for retinal homeostasis. How this secretome changes in diabetic eyes treated with anti-vascular endothelial growth factor (VEGF) inhibitors is unclear.
Methods: Diabetic conditions were simulated in vitro using ARPE-19 cell-line culture, with high glucose (25mM) culture media and hypoxia was chemically induced using cobalt chloride. Stress was assessed using cell viability assays as well as Western blots and enzyme-linked immunosorbent assay (ELISA) for production of HIF-1a and VEGF-A. Production of neurotrophic factors was quantified once conditions were established using ELISA under stress with and without the addition of VEGF inhibitors. Changes were analysed with one-way ANOVA.
Results: Hypoxia downregulated pigment epithelium derived factor (PEDF) expression. The addition of bevacizumab, ranibizumab and aflibercept in normoxic conditions all led to a significant downregulation of PEDF. Glucose concentration had no effect on secretion of PEDF. Brain derived neurotrophic factor (BDNF) secretion was downregulated in high glucose and was upregulated in hypoxia. Placental growth factor (PlGF) secretion by ARPE-19 was undetectable by ELISA.
Conclusions: We found that hypoxia, high glucose or VEGF inhibitors affected secretion of neurotrophic factors. This variation under different conditions may influence neuron and photoreceptor survival in the diabetic state and VEGF inhibitor treated eyes.
PMID: 31265210 DOI: 10.1111/ceo.13579
Retina. 2019 Jun 11.
Efficacy and safety of a treat-and-extend regimen with aflibercept in treatment-naive patients with type 3 neovascularization: A 52-week, single-arm, multicenter trial.
Arias L, Cervera E, Vilimelis JC, Escobar JJ, Escobar AG, Zapata MÁ.
Purpose: To evaluate 52-week efficacy and safety of a treat-and-extend regimen of intravitreal aflibercept 2 mg on treatment-naive Type 3 neovascularization lesions.
Methods: Phase IV, prospective, open-label, single-arm, multicenter trial including patients with untreated Stage I/II Type 3 neovascularization lesions and baseline best-corrected visual acuity between 78 and 23 Early Treatment Diabetic Retinopathy Study letters. Primary endpoint: mean change in best-corrected visual acuity from baseline at 52 weeks.
Results: Thirty-two eyes from 32 patients were included (mean ± SD age: 78.2 ± 7.7 years, 68.8% females, baseline best-corrected visual acuity: 57.9 ± 15.4 [Snellen fraction 20/70]). Best-corrected visual acuity increased by 10.5 ± 15.9 Early Treatment Diabetic Retinopathy Study letters at Week 52 (P = 0.0001). The mean foveal and choroidal thickness decreased by 129.1 ± 80.1 µm (P < 0.0001) and 64.3 ± 96.5 (P = 0.0001), respectively. The proportion of patients with intraretinal/subretinal fluid decreased from 28 (87.5%) at baseline to 3 (11.5%) at Week 52 (P < 0.0001). Pigment epithelial detachment and lesion area showed nonsignificant changes over 52 weeks. The mean number of injections was 8.0 ± 2.0. Seven (21.9%) patients experienced treatment-related adverse events and two (6.3%) experienced serious adverse events; one (3.1%) ocular serious adverse event requiring treatment withdrawal, endophthalmitis, and one (3.1%) nonocular spontaneously resolved serious adverse event, palpitations. One (3.1%) patient experienced an APTC ATE: nonfatal stroke not related to trial treatment.
Conclusion: A treat-and-extend regimen of aflibercept improves visual acuity and retinal edema in eyes with Type 3 neovascularization over 52 weeks with good tolerability.
PMID: 31259813 DOI: 10.1097/IAE.0000000000002582
JAMA Ophthalmol. 2019 Jul 11.
Incidence of new choroidal neovascularization in fellow eyes of patients with age-related macular degeneration treated with intravitreal aflibercept or ranibizumab.
Parikh R, Avery RL, Saroj N, Thompson D, Freund KB.
Importance: Incidence of conversion to neovascular age-related macular degeneration (nAMD) in untreated fellow eyes of patients who are treated for nAMD in 1 eye with anti-vascular endothelial growth factor agents provides important prognostic information to clinically manage patients.
Objective: To investigate the association of treatment assignment (intravitreal aflibercept vs ranibizumab) and baseline characteristics with fellow eye conversion to nAMD in the VEGF (Vascular Endothelial Growth Factor) Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies.
Design, Setting and Participants: This post hoc analysis of the VIEW 1 and VIEW 2 studies (randomized, double-masked, active-controlled, multicenter, 96-week, phase 3 trials comparing the efficacy and safety of intravitreal aflibercept in 2457 patients with treatment-naive eyes with nAMD) analyzed a subgroup of participants treated for nAMD in 1 eye who had untreated fellow eyes without neovascularization at baseline. All participants in the VIEW studies were included in 1 of 4 groups: ranibizumab, 0.5 mg, every 4 weeks; aflibercept, 2 mg, every 4 weeks; aflibercept, 0.5 mg, every 4 weeks; or aflibercept, 2 mg, every 8 weeks after 3 injections at 4-week intervals. Data collection in the VIEW studies occurred from July 2007 to August 2011; the data analysis presented in this report took place from April 2016 to November 2018.
Interventions: Patients received no treatment in the fellow eyes unless after conversion to nAMD, when any treatment approved by heath authorities was given per the investigators' discretion.
Main Outcomes and Measures: Incidence of conversion to nAMD in patients with untreated fellow eyes that had not had clinical signs of neovascularization at baseline.
Results: A total of 1561 participants were included in this analysis. At 96 weeks, 375 patients (24.0%) experienced cases of conversion to neovascular disease in the fellow eye, including 107 of the 399 individuals who received ranibizumab, 0.5 mg, every 4 weeks; 93 of the 387 individuals who received aflibercept, 2 mg, every 4 weeks; 84 of the 387 individuals who received aflibercept, 0.5 mg, every 4 weeks; and 91 of the 388 individuals who received aflibercept, 2 mg, every 8 weeks after 3 doses at 4-week intervals. The rates were 18.1, 16.2, 14.7, and 16.0 per 100 patient-years at risk at week 96, respectively. On multivariate analysis, fellow eye conversion was associated with increasing patient age (per 10 years) at baseline (hazard ratio [HR], 1.20 [95% CI, 1.05-1.36]), female sex (HR, 1.32 [95% CI, 1.06-1.63]), intraretinal fluid in the study eye at baseline (HR, 1.28 [95% CI, 1.02-1.61]), and increasing choroidal neovascularization lesion size (per 10 mm2) in the study eye at baseline (HR, 1.29 [95% CI, 1.06-1.57]). Rates of fellow eye conversion were similar with either of the treatments.
Conclusions and Relevance: In this secondary analysis of randomized clinical trial data, patients with active nAMD in 1 eye appeared to have a high risk for fellow eye conversion. Such patients should be monitored closely.
PMID: 31294771 DOI: 10.1001/jamaophthalmol.2019.1947
Imaging
Transl Vis Sci Technol. 2019 Jun 27;8(3):50.
Pseudoflow with OCT angiography in eyes with hard exudates and macular drusen.
Hou KK, Au A, Kashani AH, Freund KB, Sadda SR, Sarraf D.
Purpose: To analyze "pseudoflow," a false positive flow-artifact observed with optical coherence tomography angiography (OCTA) of stationary hyperreflective structures corresponding to hard exudates and macular drusen.
Methods: Retrospective case series of patients with hard exudates (due to diabetic macular edema [DME] or retinal vein occlusion [RVO]) or macular drusen (due to nonneovascular, or dry, age-related macular degeneration [AMD]) studied with OCTA by using volume-based projection artifact removal (3D PAR).
Results: OCTA of 20 eyes (10 DME/10 RVO) with hard exudates were analyzed. All eyes exhibited pseudoflow corresponding to hard exudates. Seven eyes concurrently demonstrated hard exudates without pseudoflow that were noted in areas lacking vascular flow in the overlying retina. Eight eyes exhibited suspended scattering particles in motion. In 26 of 30 eyes with nonneovascular AMD, pseudoflow associated with macular drusen of any type was noted. Two of 11 eyes with small drusen, 16 of 17 eyes with medium or large drusen, 5 of 5 eyes with drusenoid pigment epithelial detachment, 12 of 16 eyes with ribbon-like subretinal drusenoid deposits, and 13 of 17 eyes with dot-like SDD exhibited pseudoflow.
Conclusions: Pseudoflow due to projection artifact is common in eyes with hard exudates or macular drusen. 3D PAR reduces but does not eliminate pseudoflow, and pseudoflow may be detected within the foveal avascular zone, indicating that other factors, such as Z-axis micromotion, may also contribute to pseudoflow.
Translational Relevance: This study provides insight into the etiology of pseudoflow noted on OCTA and will guide more accurate clinical interpretation and investigation of OCTA images.
PMID: 31293805 PMCID: PMC6601711 DOI: 10.1167/tvst.8.3.50
Pathogenesis
Eye (Lond). 2019 Jul 2.
Early local activation of complement in aqueous humour of patients with age-related macular degeneration.
Altay L, Sitnilska V, Schick T, Widmer G, Duchateau-Nguyen G, Piraino P, Jayagopal A, Drawnel FM, Fauser S.
Objective: To investigate complement activation in aqueous humour of patients with early, intermediate and neovascular age-related macular degeneration (AMD).
Patients and Methods: Aqueous humour of 79 AMD patients (early, intermediate and neovascular) and 77 age-matched controls was prospectively collected. The levels of the complement protein 3 (C3), activation products complement factor 3a (C3a) and Ba, C3b/iC3b, complement factors B, H and I (CFB, CFH and CFI), and total protein concentration were measured. Data were modelled using covariate analysis to assess the impact of age and glaucoma status of patients and total protein concentration of samples on complement protein concentration across groups.
Results: C3a concentration was significantly increased in the aqueous humour of early (p = 0.016), intermediate (p = 0.003) and neovascular (p = 0.018) AMD patients, whilst C3 concentration was significantly increased in early AMD patients only (p = 0.019). Levels of CFB and CFH were significantly increased in the aqueous humour of neovascular AMD patients (p = 0.023 and p = 0.018, respectively).
Conclusions: Our findings provide evidence for early local complement dysregulation in AMD patients, suggesting that complement pathway inhibition may be a clinically relevant intervention for early stages of AMD.
PMID: 31267090 DOI: 10.1038/s41433-019-0501-4
Metabolites. 2019 Jul 2;9(7). pii: E127.
Human plasma metabolomics in age-related macular degeneration: meta-analysis of two cohorts.
Laíns I, Chung W, Kelly RS, Gil J, Marques M, Barreto P, Murta JN, Kim IK, Vavvas DG, Miller JB, Silva R, Lasky-Su J, Liang L, Miller JW, Husain D.
Abstract: The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 × 10-2-1.8 × 10-5), and 67 across disease stages (FDR q-value: 4.5 × 10-2-1.7 × 10-4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value ≤ 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition.
PMID: 31269701 DOI: 10.3390/metabo9070127
Stem cells
Ophthalmol Retina. 2019 Apr 26. pii: S2468-6530(19)30090-9.
Evaluation of transplanted autologous induced pluripotent stem cell-derived retinal pigment epithelium in exudative age-related macular degeneration.
Takagi S, Mandai M, Gocho K, Hirami Y, Yamamoto M, Fujihara M, Sugita S, Kurimoto Y, Takahashi M.
Purpose: To report the results after 4 years of follow-up in a previously presented first case of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet autologous transplantation using multimodal imaging.
Design: Follow-up of a single case.
Participant: A patient with exudative age-related macular degeneration and polypoidal choroidal vasculopathy.
Methods: Transplantation of an autologous iPSC-derived RPE cell sheet after removal of choroidal neovascularization (CNV) in September 2014.
Main Outcome Measures: The function of the graft was assessed 4 years after surgery by color fundus photography, spectral-domain (SD) OCT, fluorescein angiography, indocyanine green angiography, and an adaptive optics (AO) retinal camera.
Results: At the 4-year follow-up, the transplanted autologous iPSC-derived RPE sheet had survived beneath the retina with slight expansion of the pigmented area and no adverse events. The outer nuclear layer above and adjacent to the graft showed acceptable thickness and an organized structure. Fluorescein angiography and SD OCT suggested the presence of vessel-like structures confined to the grafted area associated with the remaining trunk vessel of preoperative polypoidal choroidal vasculopathy but with no exudative changes. Visual acuity has been stable with no additional injections of anti-vascular endothelial growth factor agent. The choroidal volume at the graft site is relatively preserved when compared with the volume outside this site without RPE after removal of the CNV. Indocyanine green angiography revealed a preserved choriocapillaris around the iPSC-derived RPE sheet. Dark cell-like structures with a predominantly hexagonal arrangement were observed by AO imaging in an area located near the margin of the graft sheet. The average intercell distance was found to be stable over time.
Conclusions: Thus far, the grafted iPSC-derived RPE sheet has survived for 4 years and seems to support photoreceptors and choroidal vessels. The morphologic characteristics of the RPE are observed at the transplant site.
PMID: 31248784 DOI: 10.1016/j.oret.2019.04.021
Cell Reprogram. 2018 Dec;20(6):329-336.
Suprachoroidal adipose tissue-derived mesenchymal stem cell implantation in patients with dry-type age-related macular degeneration and stargardt's macular dystrophy: 6-Month Follow-Up Results of a Phase 2 Study.
Oner A, Gonen ZB, Sevim DG, Smim Kahraman N, Unlu M.
Abstract: This prospective clinical case series aimed to investigate the safety and efficacy of suprachoroidal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in patients with dry-type age-related macular degeneration (AMD) and Stargardt's macular dystrophy (SMD). This study included four patients with advanced-stage dry-type AMD and four patients with SMD who underwent suprachoroidal implantation of ADMSCs. The best-corrected visual acuity (BCVA) in the study was 20/200. The worse eye of the patient was operated on. Patients were evaluated on the first day, first week, and first, third, and sixth months postoperatively. BCVA, anterior segment and fundus examination, color photography, fundus autofluorescence, optical coherence tomography, and visual field examination were carried out at each visit. Fundus fluorescein angiography and multifocal electroretinography (mf-ERG) recordings were performed at the end of the first, third, and sixth months and anytime if necessary during the follow-up. All eight patients completed the sixth month follow-up. None of them had any systemic or ocular complications. All of the eight patients experienced visual acuity improvement, visual field improvement, and improvement in mf-ERG recordings. Stem cell treatment with suprachoroidal implantation of ADMSCs seems to be safe and effective in the treatment of dry-type AMD and SMD.
PMID: 31251672 DOI: 10.1089/cell.2018.0045
Case reports
Retin Cases Brief Rep. 2019 Jul 1.
Asymetric growth of macular atrophy associated with underlying mature, nonexudative choroidal neovascularisation.
Monés J, Rodríguez-Bocanegra E, Biarnés M.
Background/Purpose: To describe a case study that shows a possible association between the slow growth rate of macular atrophy and the presence of underlying mature, nonexudative choroidal neovascularization.
Methods: Case report.
Patient: An 82-year-old woman with mixed age-related macular degeneration in both eyes was followed up for 6 years, with the last ranibizumab treatment given in the left eye more than 2 years previously. Evaluations included fluorescein angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography.
Results: During follow-up, there was a peculiar growth of macular atrophy, involving mainly the superior nasal sector. No signs of exudation on fluorescein angiography or spectral-domain optical coherence tomography were apparent throughout this period. However, optical coherence tomography angiography showed a mature, nonexudative choroidal neovascularization under the foveal sparing area and surrounding all the boundaries of atrophy except in the superonasal sector. Macular atrophy growth was observed mainly in the region devoid of blood vessels.
Conclusion: Growth of macular atrophy was more prominent in the region where mature, nonexudative choroidal neovascularization was absent. Nutrients provided by vessels from choroidal neovascularization may provide support to adjacent retinal pigment epithelium cells, slowing down the progression of atrophy.
PMID: 31274850 DOI: 10.1097/ICB.0000000000000888
Doc Ophthalmol. 2019 Jul 8.
Late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration.
Tsunoda K, Fujinami K, Yoshitake K, Iwata T.
Purpose: To report the clinical and genetic characteristics of 6 cases with late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration.
Methods: Clinical and genetic data were collected from 6 independent patients who complained of night blindness in their fifth to eighth decade of life. The ophthalmological examinations included ophthalmoscopy, fundus autofluorescence (FAF), and full-field electroretinography (ERG). Whole exome sequencing with target gene analysis was performed to determine the causative genes and variants.
Results: All of the patients first complained of night blindness at the ages of 40-71 years. Funduscopic examinations demonstrated white or atrophic flecks scattered in the posterior pole and peripheral retina bilaterally. FAF showed patchy hypo-autofluorescence spots in the posterior pole similar to that of the trickling type of age-related macular degeneration (AMD). The region of abnormal FAF rapidly expanded with age, and one eye developed a choroidal neovascularization. The full-field scotopic ERGs with 20 min of dark adaptation were severely reduced or extinguished in all cases. There was partial recovery of the ERGs after 180 min of dark adaptation. The cone ERGs were reduced in all cases. Whole exome sequencing revealed no pathogenic variants of 301 retinal disease-associated genes.
Conclusions: The six cases had some common features with the flecked retina syndrome, familial drusen, and late-onset retinal degeneration although none had pathogenic variants causative for these disorders. These cases may represent a subset of severe trickling AMD or a new clinical entity of acquired pan-retinal visual cycle deficiency of unknown etiology.
PMID: 31286363 DOI: 10.1007/s10633-019-09705-7
Med Hypothesis Discov Innov Ophthalmol. 2019 Summer;8(2):69-72.
Early miscarriage occurring six days after intravitreal ranibizumab injection.
Akkaya S.
Abstract: The aim of this case report was to describe a miscarriage which occurred 6 days after an intravitreal Ranibizumab (IVR) injection. A 24-year-old female patient with type 1 diabetes diagnosed with diabetic macular edema in her left eye planned for 3 injections of IVR at one-month intervals. She had been receiving insulin injections 3 times a day and her Hemoglobin A1C (HbA1c) was in the approximate range of 6-7%. An ophthalmologic examination revealed that the patient's Snellen corrected distance visual acuity (CDVA) was 10/10 in her right eye and 3/10 in her left eye. The patient was unaware of her pregnancy at the time of initial injection. Two days after the first injection, she found out that she was 5 weeks pregnant. This was the first pregnancy for the patient and there were no risk factors for miscarriage rather than diabetes. Six days after the injection, she was admitted to the hospital due to severe abdominal pain and vaginal bleeding. Miscarriage was diagnosed and she underwent curettage procedure. We concluded that pregnancy tests should be administered prior to intravitreal injection for female patients of reproductive age, and patient testimony should not be the sole reason to dismiss the possibility of pregnancy.
PMID: 31263715 PMCID: PMC6592307