Publications by authors named "Itay Chowers"

91 Publications

Correlation of response to intravitreal bevacizumab treatment between the first and second treated eyes in diabetic macular edema.

Eur J Ophthalmol 2021 Nov 13:11206721211059680. Epub 2021 Nov 13.

Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, 26742Hebrew University of Jerusalem, Israel.

Purpose: To evaluate whether outcome of bevacizumab treatment in the first treated eye can guide the selection of compound for the second treated eye in patients with bilateral diabetic macular edema.

Methods: Demographic, clinical, and optical coherence tomography data were retrospectively collected from consecutive patients who underwent bevacizumab therapy for bilateral diabetic macular edema. Change in central subfield thickness and visual acuity were evaluated and compared between the first treated eye and second treated eye.

Results: A total of 66 eyes of 33 patients were included in the study. The mean ± SD follow-up time was 13 ± 5 months. The mean ± SD central subfield thickness at baseline was 464 ± 30 μm in the first treated eye and 461 ± 29 μm in the second treated eye ( = 0.91). Final central subfield thickness was reduced to 392 ± 27 μm in the first treated eye ( = 0.01 compared with baseline) and 416 ± 25 μm in the second treated eye ( = 0.03 compared with baseline). Using ≥5% or ≥10% reduction of central subfield thickness as diagnostic criteria to predict similar magnitude of thickness reduction in the first treated eye yielded a positive and negative predictive value ranging from 46% to 81%, and sensitivity and specificity ranging from 54% to 84%. Regression models did not show correlation between central subfield thickness reduction in first treated eye and the second treated eye at the end of follow-up.

Conclusions: Bevacizumab therapy reduced macular thickness in both eyes in bilateral diabetic macular edema. Treatment outcome of the first treated eye could not predict the outcome of the second treated eye. Particularly, failure to reduce central subfield thickness in the first treated eye does not preclude a favorable response to bevacizumab therapy in the second eye.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/11206721211059680DOI Listing
November 2021

Autoimmune retinopathy: clinical, electrophysiological, and immunological features in nine patients with long-term follow-up.

Graefes Arch Clin Exp Ophthalmol 2021 Sep 30. Epub 2021 Sep 30.

Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, POB 12000, 91120, Jerusalem, Israel.

Purpose: We aim to report on the clinical, imaging, immunological, and electrophysiological features of patients with autoimmune retinopathy (AIR) with long-term follow-up.

Methods: Single-center, retrospective study of a consecutive group of AIR patients treated in a tertiary academic medical center.

Results: Included were nine patients with a mean ± SD age at presentation of 65 ± 13 years and a median follow-up of 63 months (range 18-120). Five patients were known to have cancer. Median interval between onset of ocular symptoms and diagnosis of AIR was 36 months. Mean baseline and final LogMAR visual acuity were 0.72 ± 0.9 and 1.1 ± 1.2, respectively (p = 0.17). The most common funduscopic findings included optic atrophy and bone-spicule-like pigmentation. Thinning of the nerve fiber layer was the most frequent optical coherence tomographic abnormality. Electroretinographic (ERG) recordings demonstrated variably reduced cone- and rod-derived amplitudes in the majority of eyes at presentation. The most commonly detected anti-retinal antibody was anti-α-enolase. Treatment included immunomodulatory therapy and plasmapheresis. ERG tests showed stability in 64% of eyes throughout the treatment period.

Conclusion: This study highlights the importance of maintaining a high index of suspicion of AIR, particularly in late middle-aged and elderly patients with "unexplained" visual loss, in light of the non-specific posterior segment signs and the inconsistency of the routinely used ancillary tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-021-05409-4DOI Listing
September 2021

Analysis of the Aqueous Humor Proteome in Patients With Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2021 08;62(10):18

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: Age-related macular degeneration (AMD) is associated with altered gene and protein expression in the retina. We characterize the aqueous humor (AH) proteome in AMD to gain insight into the pathogenesis of the disease and identify potential biomarkers.

Methods: AH was collected from age and gender matched neovascular AMD (nvAMD; n = 10) patients and controls (n = 10). AH was pooled to create two samples (nvAMD and control), followed by intensity-based label-free quantification (MS1). Functional and bioinformatic analysis were then performed. A validation set (20 controls, 15 atrophic AMD and 15 nvAMD) was tested via multiplex ELISA for nine differentially expressed proteins according to the MS1 findings.

Results: MS1 identified 674 proteins in the AH. 239 proteins were upregulated in nvAMD (nvAMD/control > 2, peptide tags (PT) > 2), and 86 proteins were downregulated (nvAMD/control < 0.5, PT > 2). Functional analysis of proteins upregulated in AMD demonstrated enrichment for platelet degranulation (enrichment score (ES):28.1), negative regulation of endopeptidase activity (ES:18.8), cellular protein metabolic process (ES:11.8), epidermal growth factor-like domain (ES:10.3), sushi/SCR/CCP (ES:10.1), and complement/coagulation cascades (ES:9.2). AMD protein clusters were upregulated for 3/6 (χ2 < 0.05 compared to randomization). Validation via ELISA confirmed MS1 in 2/9 proteins (Clusterin and Serpin A4, P < 0.05), while 3/9 showed differential expression between aAMD and nvAMD (Clusterin, Serpin A4, and TF P < 0.05). Receiver operating characteristic curve calculation identified the area under the curve of 0.82 for clusterin as a biomarker for distinction of AMD.

Conclusions: AH proteomics in AMD patients identified several proteins and functional clusters with altered expression. Further research should confirm if these proteins may serve as biomarkers or therapeutic target for the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.62.10.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374990PMC
August 2021

FULL-THICKNESS MACULAR HOLE IN AGE-RELATED MACULAR DEGENERATION PATIENTS WITH TWO DISTINCT ENTITIES: A Multicenter Study.

Retina 2021 Oct;41(10):2066-2072

Department of Ophthalmology, Meir Medical Center, Kfar Saba, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Purpose: To describe optical coherence tomography characteristics of full-thickness macular holes (FTMHs) in age-related macular degeneration patients.

Methods: A multicenter, retrospective, observational case series of patients diagnosed with age-related macular degeneration and FTMHs seen between January 1, 2009, and January 3, 2020. Clinical charts and spectral-domain optical coherence tomography images were reviewed. Optical coherence tomography findings included FTMH-inverted trapezoid or hourglass appearance, central macular thickness (CMT), complete retinal pigment epithelium and complete retinal outer retinal atrophy, and presence of pigment epithelium detachment and epiretinal membrane. The mean outcome was the morphologic and functional characterization of different subtypes of FTMHs.

Results: A total of 86 eyes of 85 consecutive patients, with mean age of 80.31 ± 8.06 and mean best-corrected visual acuity of 1.17 ± 0.58 logarithm of the minimal angle of resolution. Two different subtypes of FTMHs were identified: tractional and degenerative. Fifty (58%) degenerative FTMHs characterized with inverted trapezoid appearance and 36 (42%) tractional FTMHs characterized with hourglass appearance. Degenerative FTMHs presented with 66% of CMT < 240 µm, 14% of CMT > 320, and 70% of complete retinal outer retinal atrophy, in comparison with 41% of CMT < 240 µm, 42.9% of CMT > 320%, and 20% of complete retinal outer retinal atrophy in the tractional FTMH group (P = 0.002, 0.003, <0.001, respectively). The presence of epiretinal membrane and pigment epithelium detachment where significantly higher in tractional FTMHs (P = 0.02, 0.03, respectively).

Conclusion: Degenerative and tractional FTMHs may be two distinct clinical entities. Discerning degenerative from tractional FTMHs is possible by using optical coherence tomography features including shape of the FTMHs, CMT, internal-external ratio of FTMHs, and presence of complete retinal outer retinal atrophy, pigment epithelium detachment, and epiretinal membrane.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0000000000003141DOI Listing
October 2021

Long-term outcome of neovascular age-related macular degeneration: association between treatment outcome and major risk alleles.

Br J Ophthalmol 2021 Jun 2. Epub 2021 Jun 2.

Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel

Aims: To evaluate the long-term functional and anatomical outcomes of neovascular age-related macular degeneration (nvAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) for up to 10 years, and to identify associated risk factors.

Methods: Clinical and optical coherence tomography findings were retrieved for nvAMD cases treated with intravitreal anti-VEGF compounds using a treat-and-extend protocol. In addition, the major risk alleles for AMD in the (rs1061170), (rs1200638) and (rs2230199) genes were genotyped.

Results: From 276 eligible eyes in 206 patients, 80 eyes (29%) in 66 patients (32.0%) had a follow-up period of ≥8 years and were included in this study. Over a 10-year period, 73.3±28.0 (mean±SD) anti-VEGF injections were administered. Best-corrected visual acuity (BCVA; LogMAR) deteriorated from 0.55±0.53 at baseline to 1.00±0.73 at 10 years (p<0.0005). Central subfield thickness (CST) decreased from 415.8±162.1 µm at baseline to 323±113.6 µm (p<0.0005) after three monthly injections and remained lower than baseline throughout the follow-up period. Visual outcome was associated with BCVA and intraretinal fluid (IRF) at baseline, macular atrophy, and macular thinning at follow-up. The decrease in CST was inversely correlated with the number of and/or risk alleles carried by the patient (Pearson's r: -0.608; p=0.003).

Conclusions: Patients with nvAMD who received anti-VEGF therapy for 10 years developed substantial vision loss associated with the presence of IRF at baseline and macular atrophy. Major risk alleles for AMD in two complement genes were associated with a reduced long-term reduction in macular thickness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2021-319054DOI Listing
June 2021

Outcomes of primary rhegmatogenous retinal detachment repair among young adult patients.

Acta Ophthalmol 2021 Dec 4;99(8):892-897. Epub 2021 Feb 4.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: To evaluate the functional and anatomical outcomes of primary rhegmatogenous retinal detachment (RRD) repair in young adults.

Methods: A retrospective, comparative case series study. Patients between the ages of 18 and 40 years who underwent surgical repair of primary RRD between the years 2006 and 2013 were included. Patients were divided into three groups according to the surgical technique used: scleral buckle (SB), pars plana vitrectomy (PPV) or combined surgery (SB-PPV).

Results: Ninety eyes (90 patients) were included. The mean age (SD) was 31.5 ± 5.1 years (range 22-40). Sixty-seven patients underwent SB, 10 had PPV and 13 had SB-PPV. Anatomical success rates were similar between the three groups (87%, 90% and 85% for SB, PPV and SB-PPV groups, respectively; p-value = 0.9). Mean (SD) preoperative LogMAR visual acuity (VA) was 0.46 ± 0.6, 1.73 ± 1.1, 1.1 ± 1.1 for SB, PPV and SB-PPV groups, respectively (p < 0.0001). The VA improved at last follow-up to 0.23 ± 0.4, 0.7 ± 1.5 and 1.09 ± 1.08 in SB, PPV and SB-PPV groups, respectively (p < 0.0001). Macula-off was diagnosed in 19.4% of SB, 80% of PPV and 53.9% of SB-PPV groups (p < 0.0001). In the SB group one phakic patient (1.5%) needed cataract extraction, while following PPV, all phakic eyes (100%) underwent cataract extraction eventually (p-value < 0.0001).

Conclusions: The study emphasizes the efficacy of SB as a primary procedure for the repair of retinal detachment in young adults in terms of anatomical and functional success. Furthermore, preservation of the lens as a result of using SB rather than PPV when possible is of great importance in this age group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14783DOI Listing
December 2021

Hybrid Telehealth Medical Retina Clinic Due to Provider Exposure and Quarantine During COVID-19 Pandemic.

Clin Ophthalmol 2020 21;14:3421-3426. Epub 2020 Oct 21.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Objective: To present our hybrid telehealth medical retina clinic service with intravitreal injections (IVI) treatment as a safe alternative to in-person visits and examination during COVID-19 pandemic disease.

Methods: Due to exposure to a COVID-19 positive retina fellow, our retina service, in quarantine, evaluated patients' medical files and retinal scans using a telemedicine approach. A different protocol for patients coming for IVI during the COVID-19 pandemic was established for IVI administration.

Results: During the 14-day quarantine period (between March 18th and March 31st 2020), the hybrid telehealth medical retina clinic performed 523 IVI to 394 patients with a mean age ± SD 70.96 ± 14.4 years. IVI were administered for neovascular age-related macular degeneration in 50.5% of the cases (199 patients), diabetic macular edema in 21.3% (84 patients), retinal vein occlusion in 17.5% (69 patients), and 10.7% for other retinal pathologies (42 patients). No ocular or systemic complications were observed.

Conclusion: During disasters and pandemics, IVI can be provided safely using a hybrid telehealth medical retina clinic approach but only in the appropriate patient and health care system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OPTH.S276276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585855PMC
October 2020

Unique combination of clinical features in a large cohort of 100 patients with retinitis pigmentosa caused by FAM161A mutations.

Sci Rep 2020 09 16;10(1):15156. Epub 2020 Sep 16.

Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University Jerusalem, Jerusalem, Israel.

FAM161A mutations are the most common cause of autosomal recessive retinitis pigmentosa in the Israeli-Jewish population. We aimed to characterize the spectrum of FAM161A-associated phenotypes and identify characteristic clinical features. We identified 114 bi-allelic FAM161A patients and obtained clinical records of 100 of these patients. The most frequent initial symptom was night blindness. Best-corrected visual acuity was largely preserved through the first three decades of life and severely deteriorated during the 4th-5th decades. Most patients manifest moderate-high myopia. Visual fields were markedly constricted from early ages, but maintained for decades. Bone spicule-like pigmentary changes appeared relatively late, accompanied by nummular pigmentation. Full-field electroretinography responses were usually non-detectable at first testing. Fundus autofluorescence showed a hyper-autofluorescent ring around the fovea in all patients already at young ages. Macular ocular coherence tomography showed relative preservation of the outer nuclear layer and ellipsoid zone in the fovea, and frank cystoid macular changes were very rare. Interestingly, patients with a homozygous nonsense mutation manifest somewhat more severe disease. Our clinical analysis is one of the largest ever reported for RP caused by a single gene allowing identification of characteristic clinical features and may be relevant for future application of novel therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-72028-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495424PMC
September 2020

Correlation of Response between Both Eyes to First- and Second-Line Anti-VEGF Therapy in Diabetic Macular Edema.

Curr Eye Res 2021 04 30;46(4):539-545. Epub 2020 Aug 30.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: To evaluate the anatomical correlation between fellow eyes for bilateral second-line anti-VEGF treatment in eyes with bilateral diabetic macular edema (DME) with incomplete response to first-line bevacizumab therapy.

Methods: Seventy-four eyes ( = 37 patients) with bilateral-DME having incomplete response to first-line bevacizumab therapy that were switched for bilateral treatment with ranibizumab were retrospectively evaluated. Data collected included demographics, visual acuity and macular thickness. We evaluate the correlation for the response of both eyes in terms of macular thickness and visual acuity.

Results: The mean±SD age was 76 ± 8 years. The mean±SD number of bevacizumab injections prior the switch was 11.03 ± 5.1 in the first eye (FE) and 10.9 ± 5.2 in the second eye (SE). The central subfield thickness (CST) reduced from 472 ± 171 microns at baseline to 418 ± 161 after the last bevacizumab injection and 365 ± 74 after 3 ranibizumab injections in the FE ( = .016, = .004, respectively), and from 463 ± 145 microns to 446 ± 123, and 421 ± 103 in the SE ( = .112, = .001, respectively). There was strong positive correlation between the eyes for the CST reduction under bevacizumab and ranibizumab treatments in each visit. BCVA± SD at baseline was 0.41 ± 0.30 LogMAR in the FE, and 0.42 ± 0.29 in the SE ( = .44). After 3 injections of bevacizumab, the BCVA was 0.37 ± 0.26 and 0.42 ± 0.23 in FE and SE respectively ( = .013, = .132, respectively).

Conclusions: This study demonstrated a strong anatomical correlation responses between the eyes in patients with bilateral DME for both first-line bevacizumab therapy and second-line ranibizumab therapy. Response to second-line therapy was favorable and correlated among eyes regardless they were from the same or different individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2020.1812085DOI Listing
April 2021

The ethical advantages of video conferencing in medical education.

Med Educ Online 2020 12;25(1):1787310

Department of Ophthalmology, Hadassah Medical Center , Jerusalem, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10872981.2020.1787310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482868PMC
December 2020

Risk of SARS-CoV-2 transmission to medical staff and patients from an exposure to a COVID-19-positive ophthalmologist.

Graefes Arch Clin Exp Ophthalmol 2020 Oct 21;258(10):2271-2274. Epub 2020 Jun 21.

Department of Ophthalmology, Hadassah Medical Center and the Hebrew University - Hadassah School of Medicine, PO Box 12000, 91120, Jerusalem, Israel.

Purpose: To evaluate the risk of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after exposure to a COVID-19+ physician in a retina clinic.

Methods: A retrospective observational study. Records of 142 patients and 11 staff members from a single retina clinic that were exposed to a COVID-19+ ophthalmologist were reviewed. All 153 individuals were placed in quarantine for 14 days. They were contacted after the quarantine period to inquire about symptoms consistent with COVID-19, and the results of diagnostic test for SARS-CoV-2 when performed.

Results: All patients (n = 142) were contacted successfully. The mean age was 72.8 ± 13.6 years; 54.2% (n = 77) were females. Twenty-three patients (16.2%) were exposed during an ophthalmic exam, 111 (78.2%) during intraocular injection, 4 (2.8%) underwent exam and injection, 3 (2.1%) underwent surgery, and one patient (0.7%) had laser photocoagulation. Half of the patients (50%; n = 71) were in contact with the COVID-19+ physician while he was symptomatic. Forty-four patients (31%) wore a mask on the day of their visit. 11.3% (n = 16) of the patients, and all involved staff had been tested for the virus and all were negative. One patient (0.7%) reported transient cough and sore throat, and the remaining 141 (99.3%) patients and 11 (100%) staff did not develop symptoms.

Conclusions: Low risk for SARS-CoV-2 transmission in the ophthalmic setting was observed when universal safety measures such as social distancing, meticulous hand hygiene, enlarged breath shields, and mask wear during procedures were taken.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-020-04790-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306185PMC
October 2020

Ophthalmology practice during the COVID-19 pandemic.

BMJ Open Ophthalmol 2020 19;5(1):e000487. Epub 2020 Apr 19.

Ophthalmology Department, Hadassah Medical Center, Jerusalem, Israel.

Objective: To present an established practice protocol for safe and effective hospital-setting ophthalmic practice during the coronavirus disease 2019 (COVID-19) pandemic.

Methods And Analysis: Literature was reviewed to identify articles relevant to COVID-19 pandemic and ophthalmology. The following keywords were used: COVID-19, SARS-CoV-2 and telemedicine, combined with eye, ophthalmology, conjunctivitis and tears. Data were extracted from the identified manuscripts and discussed among subspecialists to obtain consensus evidence-based practice.

Results: A protocol for ophthalmic practice in the era of COVID-19 pandemic was established. The protocol covered patient screening, clinic flow, required personal protective equipment and modifications of ophthalmic equipment for improved safety.

Conclusion: Important literature emerged with respect to the practice of ophthalmology in the era of COVID-19. An evidence-based ophthalmic practice protocol was established and should be modified in the future to accommodate new insights on the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjophth-2020-000487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222613PMC
April 2020

Current safety preferences for intravitreal injection during COVID-19 pandemic.

Eye (Lond) 2020 Jul 4;34(7):1165-1167. Epub 2020 May 4.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41433-020-0925-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197242PMC
July 2020

Socioeconomic status and visual outcome in patients with neovascular age-related macular degeneration.

Eur J Ophthalmol 2021 May 4;31(3):1094-1100. Epub 2020 May 4.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: Visual outcome in patients with neovascular age-related macular degeneration is variable. We aimed to evaluate for association between socioeconomic status visual acuity in neovascular age-related macular degeneration.

Methods: A retrospective single-center study of a consecutive group of neovascular age-related macular degeneration patients was performed. Socioeconomic status was determined for each patient based on the 2008 Israeli census. Medical information was extracted from medical records and included visual acuity and optical coherence tomography parameters. Associations between socioeconomic status and clinical outcomes were analyzed.

Results: A total of 233 patients were included in the analysis. A correlation was found between low baseline visual acuity of the first eye diagnosed with neovascular age-related macular degeneration and low socioeconomic status (r = -0.13, p = 0.049; n = 233). The difference between the visual acuity of the lowest and the highest socioeconomic status categories at baseline was approximately 3 ETDRS lines (p = 0.048). Socioeconomic status and baseline visual acuity of the second eye of the same individual with neovascular age-related macular degeneration were not correlated (r = -0.05, p = 0.95). Socioeconomic status was not associated with the number of anti-vascular endothelial growth factor injections of the first or second eye, or the visual acuity outcome of the first or second eye after 1 year of therapy (p = 0.421, p = 0.9, respectively). Central subfield thickness of the first eye at presentation as measured by spectral-domain optical coherence tomography was associated with socioeconomic status (r = -0.31 p = 0.001).

Conclusion: Individuals of lower socioeconomic status presented at more advanced stage of the disease when developing neovascular age-related macular degeneration in the first eye but not in the second eye. The research underscores the importance of improving referral patterns and awareness for the lowest socioeconomic status classes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1120672120920783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369906PMC
May 2021

A 12-month prospective study to evaluate the efficacy of using the treat-and-extend regimen with intravitreal aflibercept as a Second-Line Treatment for Diabetic Macular Oedema (the TADI Study).

Eye (Lond) 2021 02 29;35(2):559-567. Epub 2020 Apr 29.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, and the Hebrew University - Hadassah School of Medicine, Jerusalem, Israel.

Purpose: To evaluate the efficacy of intravitreal aflibercept as a second-line therapy in eyes with persistent diabetic macular oedema (DMO) despite receiving initial bevacizumab treatment.

Methods: A prospective multicentre study was conducted in nine academic clinics in Israel. Starting from the first follow-up visit, a treat-and-extend regimen was applied in which the treatment intervals were extended by 2 weeks based on macular thickness using SD-OCT. The primary outcome was central subfield thickness (CST) at week 52.

Results: Forty-four patients (n = 48 eyes) were recruited to the study, and 43 eyes completed 52 weeks of follow-up. Patients received a mean (±SD) of 7.9 ± 3.5 bevacizumab injections before enrolment. The mean (±SD) CST under aflibercept therapy decreased from 468 ± 131 μm at baseline to 303 ± 67 μm at 52 weeks (p = 0.002), and best corrected visual acuity improved from 64 ± 15 ETDRS letters at baseline to 75 ± 8 letters at week 52 (p = 0.001). Twenty (46%) eyes met the treat-and-extend criteria and received a mean (±SD) of 10.9 ± 2 aflibercept injections.

Conclusions: Eyes with persistent DMO following initial bevacizumab therapy had a marked reduction in macular thickness and improved visual acuity following 1 year of treatment with intravitreal aflibercept. Less than half of the patients met eligibility criteria for extension of the treatment interval; for these patients, the treat-and-extend regimen resulted in a maximum treatment interval of 10 weeks during the first year.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41433-020-0901-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027790PMC
February 2021

Association of a Variant in VWA3A with Response to Anti-Vascular Endothelial Growth Factor Treatment in Neovascular AMD.

Invest Ophthalmol Vis Sci 2020 02;61(2):48

,.

Purpose: Anti-vascular endothelial growth factor (VEGF) therapy for neovascular AMD (nvAMD) obtains a variable outcome. We performed a genome-wide association study for anti-VEGF treatment response in nvAMD to identify variants potentially underlying such a variable outcome.

Methods: Israeli patients with nvAMD who underwent anti-VEGF treatment (n = 187) were genotyped on a whole exome chip containing approximately 500,000 variants. Genotyping was correlated with delta visual acuity (deltaVA) between baseline and after three injections of anti-VEGF. Top principal components, age, and baseline VA were included in the analysis. Two lead associated variants were genotyped in an independent validation set of patients with nvAMD (n = 108).

Results: Linear regression analysis on 5,353,842 variants revealed five exonic variants with an association P value of less than 6 × 10-5. The top variant in the gene VWA3A (P = 1.77 × 10-6) was tested in the validation cohort. The minor allele of the VWA3A variant was associated with worse response to treatment (P = 0.02). The average deltaVA of discovery plus validation was -0.214 logMAR (≈ a gain of 10.7 Early Treatment Diabetic Retinopathy Study letters) for homozygote for the major allele, 0.172 logMAR for heterozygotes (≈ a loss of 8.6 Early Treatment Diabetic Retinopathy Study letters), and 0.21 logMAR for homozygote for the minor allele (≈ a loss of 10.5 Early Treatment Diabetic Retinopathy Study letters). Minor allele carriers had a higher frequency of macular hemorrhage at baseline.

Conclusions: An VWA3A gene variant was associated with worse response to anti-VEGF treatment in Israeli patients with nvAMD. The VWA3A protein is a precursor of the multimeric von Willebrand factor which is involved in blood coagulation, a system previously associated with nvAMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.61.2.48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329947PMC
February 2020

Acquired unilateral visual deterioration: More to ischemia than meets the eye.

Surv Ophthalmol 2020 Nov - Dec;65(6):740-743. Epub 2019 Dec 27.

Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, California, USA.

A 56-year-old woman presented with visual loss in the right eye with best-corrected visual acuity of 20/40. Funduscopic examination revealed neovascularization of the disk with peripapillary preretinal hemorrhages and leakage on fluorescein angiography. Cerebral arteriography demonstrated stenosis of the major cerebral vessels with classic collaterals configuring as "puff of smoke." A diagnosis of moyamoya-related ocular ischemic syndrome manifesting with optic disk neovascularization was made.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.survophthal.2019.12.004DOI Listing
July 2021

Evaluation of antioxidant treatments for the modulation of macrophage function in the context of retinal degeneration.

Mol Vis 2019 5;25:479-488. Epub 2019 Sep 5.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, and the Hebrew University - Hadassah School of Medicine.

Purpose: Oxidative stress and macrophages have been implicated in the pathogenesis of atrophic and neovascular age-related macular degeneration (aAMD and nvAMD). It is unclear whether oxidative injury mediates macrophage involvement in AMD. We aimed to investigate the effect of antioxidant treatments on human monocyte-derived macrophages (hMDMs) from patients with AMD in models for the disease.

Methods: Four antioxidant treatments were evaluated (G1: lutein + zeaxanthin, G2: lutein + zeaxanthin and zinc, G3: lutein + zeaxanthin, zinc, Lyc-O-Mato, and carnosic acid, G4: lutein + zeaxanthin, carnosic acid, and beta-carotene, G5: olive oil as vehicle control). The compounds were added to the culture medium of M1 (interferon-gamma [IFN-Ɣ] and [LPS]) and M2a (interleukin-13 [IL-13] and IL-4) hMDMs from patients with AMD (n=7 and n=8, respectively). Mouse choroidal tissue was cultured with supernatants from treated M1/M2a hMDMs, to evaluate the effect of treatments on the angiogenic properties of macrophages with choroidal sprouting assay (CSA). Mouse retinal explants were cultured with treated hMDMs for 18 h, and evaluated for photoreceptor apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) labeling. Adult BALB/c mice (n=8) were exposed to 8,000 lux bright light for 3 h, and treated orally with antioxidant supplements for 7 days that preceded light injury and following it. Oxidative stress was assessed using an anti-4 hydroxynonenal (4-HNE) antibody. Retinal function and the thickness of the outer nuclear layer were evaluated with electroretinography (ERG) and histological analysis, respectively.

Results: The G3 treatment reduced M2a hMDMs-associated sprouting in the CSA compared to the untreated group (n=7, -1.52-fold, p=0.05). Conversely, the G2 treatment was associated with an increased neurotoxic effect of M2a hMDMs in the retinal explant assay compared to the control group (n=7, 1.37-fold, p=0.047), as well as compared to the G3 treatment group (1.46-fold, p=0.01). The G4 treatment was also associated with increased cytotoxicity compared to the control group (1.48-fold, p=0.004), and compared to the G3 treatment group (1.58-fold, p=0.001). In the in vivo light damage model, mice (n=8) supplemented with G2, G3, and G4 had decreased levels of oxidative injury assessed using 4-HNE labeling (-2.32-fold, -2.17-fold, and -2.18-fold, respectively, p<0.05 for all comparisons). None of the treatments were associated with reduced photoreceptor cell loss, as shown with histology and ERG.

Conclusions: Antioxidant treatment modulates M2a hMDMs at the functional level. In particular, we found that the G3 combination has a beneficial effect on M2a macrophages in reducing their angiogenic and neurotoxic capacity ex vivo. In addition, antioxidant treatments considerably reduced the oxidative stress level in light-damaged retinas. Further research is required to assess whether such therapies may curb macrophage-driven photoreceptor loss and neovascularization in AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776439PMC
April 2020

Promiscuous Chemokine Antagonist (BKT130) Suppresses Laser-Induced Choroidal Neovascularization by Inhibition of Monocyte Recruitment.

J Immunol Res 2019 5;2019:8535273. Epub 2019 Aug 5.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, P.O.B 12000, Israel.

Background: Age-related macular degeneration (AMD), the most common cause of blindness in the developed world, usually affects individuals older than 60 years of age. The majority of visual loss in this disease is attributable to the development of choroidal neovascularization (CNV). Mononuclear phagocytes, including monocytes and their tissue descendants, macrophages, have long been implicated in the pathogenesis of neovascular AMD (nvAMD). Current therapies for nvAMD are based on targeting vascular endothelial growth factor (VEGF). This study is aimed at assessing if perturbation of chemokine signaling and mononuclear cell recruitment may serve as novel complementary therapeutic targets for nvAMD.

Methods: A promiscuous chemokine antagonist (BKT130), aflibercept treatment, or combined BKT130+aflibercept treatment was tested in an laser-induced model of choroidal neovascularization (LI-CNV) and in an ex vivo choroidal sprouting assay (CSA). Quantification of CD11b+ cell in the CNV area was performed, and mRNA levels of genes implicated in CNV growth were measured in the retina and RPE-choroid.

Results: BKT130 reduced the CNV area and recruitment of CD11b+ cells by 30-35%. No effect of BKT130 on macrophages' proangiogenic phenotype was demonstrated ex vivo, but a lower and expression was found in the RPE-choroid and a lower expression of and was found in both RPE-choroid and retinal tissues in the LI-CNV model under treatment with BKT130.

Conclusions: Targeting monocyte recruitment via perturbation of chemokine signaling can reduce the size of experimental CNV and should be evaluated as a potential novel therapeutic modality for nvAMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/8535273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701410PMC
January 2020

The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies.

Acta Ophthalmol 2019 Sep 29;97(6):e877-e886. Epub 2019 Mar 29.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: To identify the accurate clinical diagnosis of rare syndromic inherited retinal diseases (IRDs) based on the combination of clinical and genetic analyses.

Methods: Four unrelated families with various autosomal recessive syndromic inherited retinal diseases were genetically investigated using whole-exome sequencing (WES).

Results: Two affected subjects in family MOL0760 presented with a distinctive combination of short stature, developmental delay, congenital mental retardation, microcephaly, facial dysmorphism and retinitis pigmentosa (RP). Subjects were clinically diagnosed with suspected Kabuki syndrome. WES revealed a homozygous nonsense mutation (c.5492dup, p.Asn1831Lysfs*8) in VPS13B that is known to cause Cohen syndrome. The index case of family MOL1514 presented with both RP and liver dysfunction, suspected initially to be related. WES identified a homozygous frameshift mutation (c.1787_1788del, p.His596Argfs*47) in AGBL5, associated with nonsyndromic RP. The MOL1592 family included three affected subjects with crystalline retinopathy, skin ichthyosis, short stature and congenital adrenal hypoplasia, and were found to harbour a homozygous nonsense mutation (c.682C>T, p.Arg228Cys) in ALDH3A2, reported to cause Sjögren-Larsson syndrome (SLS). In the fourth family, SJ002, two siblings presented with hypotony, psychomotor delay, dysmorphic facial features, pathologic myopia, progressive external ophthalmoplegia and diffuse retinal atrophy. Probands were suspected to have atypical Kearns-Sayre syndrome, but were diagnosed with combined oxidative phosphorylation deficiency-20 due to a novel suspected missense variant (c.1691C>T, p.Ala564Val) in VARS2.

Conclusion: Our findings emphasize the important complement of WES and thorough clinical investigation in establishing precise clinical diagnosis. This approach constitutes the basis for personalized medicine in rare IRDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14095DOI Listing
September 2019

A novel intronic mutation of is a major cause of autosomal recessive retinitis pigmentosa among Caucasus Jews.

Mol Vis 2019 22;25:155-164. Epub 2019 Feb 22.

Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Purpose: To identify the genetic basis for retinitis pigmentosa (RP) in a cohort of Jewish patients from Caucasia.

Methods: Patients underwent a detailed ophthalmic evaluation, including funduscopic examination, visual field testing, optical coherence tomography (OCT), and electrophysiological tests, electroretinography (ERG) and visual evoked potentials (VEP). Genetic analysis was performed with a combination of whole exome sequencing (WES) and Sanger sequencing. Bioinformatic analysis of the WES results was performed via a customized pipeline. Pathogenicity of the identified intronic variant was evaluated in silico using the web tool Human Splicing Finder, and in vitro, using a minigene-based splicing assay. Linkage disequilibrium (LD) analysis was used to demonstrate a founder effect, and the decay of LD over generations around the mutation in Caucasus Jewish chromosomes was modeled to estimate the age of the most recent common ancestor.

Results: In eight patients with RP from six unrelated families, all of Caucasus Jewish ancestry, we identified a novel homozygous intronic variant, located at position -9 of intron 15. The c.1921-9C>G variant was predicted to generate a novel acceptor splice site, nine bases upstream of the original splice site of intron 15. In vitro splicing assay demonstrated that this novel acceptor splice site is used instead of the wild-type site, leading to an 8-bp insertion into exon 16, which is predicted to cause a frameshift. The presence of a common ancestral haplotype in mutation-bearing chromosomes was compatible with a founder effect.

Conclusions: The c.1921-9C>G intronic mutation is a founder mutation that accounts for at least 40% (6/15 families) of autosomal recessive RP among Caucasus Jews. This result is highly important for molecular diagnosis, carrier screening, and genetic counseling in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386512PMC
June 2019

Deskilling in ophthalmology is the inevitable controllable?

Eye (Lond) 2019 03 24;33(3):347-348. Epub 2018 Oct 24.

Department of Ophthalmology, Hadassah Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41433-018-0252-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460715PMC
March 2019

Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel (DERBI study).

Eur J Ophthalmol 2019 Mar 19;29(2):229-233. Epub 2018 Jun 19.

13 Department of Ophthalmology, Hadassah-Hebrew University Medical Center and the Hebrew University Faculty of Medicine, Jerusalem, Israel.

Purpose:: To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab.

Methods:: Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment.

Results:: In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean (±standard deviation) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab. A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p < 0.001). Median logMAR visual acuity (±interquartile range) improved from 0.40 ± 0.48 at baseline to 0.38 ± 0.40 at month 12 (p = 0.001). Linear regression suggested that higher number of intravitreal ranibizumab injections and higher pre-switch central subfield retinal thickness were associated with favorable visual outcome. Higher number of intravitreal bevacizumab injections and the presence of intraretinal fluid before the switch lessened the odds of favorable outcome.

Conclusion:: Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1120672118782102DOI Listing
March 2019

Association of Genetic Variants With Response to Anti-Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration.

JAMA Ophthalmol 2018 08;136(8):875-884

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, England.

Importance: Visual acuity (VA) outcomes differ considerably among patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. Identification of pharmacogenetic associations may help clinicians understand the mechanisms underlying this variability as well as pave the way for personalized treatment in nAMD.

Objective: To identify genetic factors associated with variability in the response to anti-VEGF therapy for patients with nAMD.

Design, Setting, And Participants: In this multicenter genome-wide association study, 678 patients with nAMD with genome-wide genotyping data were included in the discovery phase; 1380 additional patients with nAMD were genotyped for selected common variants in the replication phase. All participants received 3 monthly injections of bevacizumab or ranibizumab. Clinical data were evaluated for inclusion/exclusion criteria from October 2014 to October 2015, followed by data analysis from October 2015 to February 2016. For replication cohort genotyping, clinical data collection and analysis (including meta-analysis) was performed from March 2016 to April 2017.

Main Outcomes And Measures: Change in VA after the loading dose of 3 monthly anti-VEGF injections compared with baseline.

Results: Of the 2058 included patients, 1210 (58.8%) were women, and the mean (SD) age across all cohorts was 78 (7.4) years. Patients included in the discovery cohort and most of the patients in the replication cohorts were of European descent. The mean (SD) baseline VA was 51.3 (20.3) Early Treatment Diabetic Retinopathy Study (ETDRS) score letters, and the mean (SD) change in VA after the loading dose of 3 monthly injections was a gain of 5.1 (13.9) ETDRS score letters (ie, 1-line gain). Genome-wide single-variant analyses of common variants revealed 5 independent loci that reached a P value less than 10 × 10-5. After replication and meta-analysis of the lead variants, rs12138564 located in the CCT3 gene remained nominally associated with a better treatment outcome (ETDRS letter gain, 1.7; β, 0.034; SE, 0.008; P = 1.38 × 10-5). Genome-wide gene-based optimal unified sequence kernel association test of rare variants showed genome-wide significant associations for the C10orf88 (P = 4.22 × 10-7) and UNC93B1 (P = 6.09 × 10-7) genes, in both cases leading to a worse treatment outcome. Patients carrying rare variants in the C10orf88 and UNC93B1 genes lost a mean (SD) VA of 30.6 (17.4) ETDRS score letters (ie, loss of 6.09 lines) and 26.5 (13.8) ETDRS score letters (ie, loss of 5.29 lines), respectively, after 3 months of anti-VEGF treatment.

Conclusions And Relevance: We propose that there is a limited contribution of common genetic variants to variability in nAMD treatment response. Our results suggest that rare protein-altering variants in the C10orf88 and UNC93B1 genes are associated with a worse response to anti-VEGF therapy in patients with nAMD, but these results require further validation in other cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2018.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142943PMC
August 2018

Centennial Anniversary of the Department of Ophthalmology of the Hadassah Medical Center, 1918-2018.

Am J Ophthalmol 2018 06 17;190:xxii-xxviii. Epub 2018 Mar 17.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2018.03.017DOI Listing
June 2018

The Genetics of Usher Syndrome in the Israeli and Palestinian Populations.

Invest Ophthalmol Vis Sci 2018 02;59(2):1095-1104

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: Usher syndrome (USH) is the most common cause for deaf-blindness. It is genetically and clinically heterogeneous and prevalent in populations with high consanguinity rate. We aim to characterize the set of genes and mutations that cause USH in the Israeli and Palestinian populations.

Methods: Seventy-four families with USH were recruited (23 with USH type 1 [USH1], 33 with USH2, seven with USH3, four with atypical USH, and seven families with an undetermined USH type). All affected subjects underwent a full ocular evaluation. A comprehensive genetic analysis, including Sanger sequencing for the detection of founder mutations, homozygosity mapping, and whole exome sequencing in large families was performed.

Results: In 79% of the families (59 out of 74), an autosomal recessive inheritance pattern could be determined. Mutation detection analysis led to the identification of biallelic causative mutations in 51 (69%) of the families, including 21 families with mutations in USH2A, 17 in MYO7A, and seven in CLRN1. Our analysis revealed 28 mutations, 11 of which are novel (including c.802G>A, c.8558+1G>T, c.10211del, and c.14023A>T in USH2A; c.285+2T>G, c.2187+1G>T, c.3892G>A, c.5069_5070insC, c.5101C>T, and c.6196C>T in MYO7A; and c.15494del in GPR98).

Conclusions: We report here novel homozygous mutations in various genes causing USH, extending the spectrum of causative mutations. We also prove combined sequencing techniques as useful tools to identify novel disease-causing mutations. To the best of our knowledge, this is the largest report of a genetic analysis of Israeli and Palestinian families (n = 74) with different USH subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.17-22817DOI Listing
February 2018

Characterizing the effect of supplements on the phenotype of cultured macrophages from patients with age-related macular degeneration.

Mol Vis 2017 6;23:889-899. Epub 2017 Dec 6.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: Oral vitamin and mineral supplements reduce the risk of visual loss in age-related macular degeneration (AMD). However, the pathways that mediate this beneficial effect are poorly understood. Macrophages may exert oxidative, inflammatory, and angiogenic effects in the context of AMD. We aim to assess if oral supplements can modulate the macrophage phenotype in this disease.

Methods: Monocytes were isolated from patients with neovascular AMD (nvAMD), cultured, matured to macrophages, and polarized to classical [M1 (stimulated by IFNγ and lipopolysaccharide (LPS))] and alternative [M2 (stimulated with IL-4 and IL-13)] phenotypes. Combinations of antioxidants including lutein+zeaxanthin (1 μM; 0.2 μM), zinc (10 µM), carnosic acid (2 µM), beta-carotene (2 µM), and standardized tomato extract containing lycopene and other tomato phytonutrients were added to the culture media. Levels of anti-inflammatory, antioxidant, and pro-angiogenic gene and protein expression were then evaluated.

Results: Combinations of lutein and carnosic acid with zinc and standardized tomato extract or with beta-carotene yielded an antioxidative, anti-inflammatory, and antiangiogenic effect in M1 and M2 macrophages. These effects manifested in the upregulation of antioxidative genes (HMOX1, SOD1) and the downregulation of pro-angiogenic genes and pro-inflammatory genes (SDF-1, TNF-alpha, IL-6, MCP-1). Lutein monotherapy or a combination of lutein and zinc had less effect on the expression of these genes.

Conclusions: Combinations of supplements can modify the expression of genes and proteins that may be relevant for the involvement of macrophages in the pathogenesis of AMD. Further studies are required to evaluate if the modulation of the macrophage phenotype partially accounts for the beneficial effect of oral supplements in AMD and if modification of the AREDS formula can improve its effect on macrophages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723149PMC
May 2018

MICROPERIMETRY IN BEST VITELLIFORM MACULAR DYSTROPHY.

Retina 2018 Apr;38(4):841-848

Department of Ophthalmology, San Raffaele Scientific Institute, University Vita-Salute, Milan, Italy.

Purpose: To investigate retinal sensitivity in eyes with all the clinical stages of Best vitelliform macular dystrophy (VMD).

Methods: Thirty-two patients affected by VMD in subclinical, vitelliform, pseudohypopyon, vitelliruptive, and atrophic stages were enrolled in this prospective cross-sectional study. Patients underwent a complete ophthalmologic examination, including determination of best-corrected visual acuity (BCVA), staging of the disease (Gass's classification), and microperimetry by means of the macular integrity assessment microperimeter. The primary outcome measure was to describe the alterations in the retinal sensitivity of eyes affected by VMD in different stages. Secondary outcome measures included correlations between retinal sensitivity and best-corrected visual acuity and the correlation between the VMD stage and the specific microperimetry pattern.

Results: Mean retinal sensitivity was reduced in all the VMD stages. Nevertheless, vitelliform, pseudohypopyon, and vitelliruptive stages turned out to be very similar, especially within 10°. Fixation was classified as stable in 27 eyes (44.2%), relatively unstable in 16 eyes (26.2%), and unstable in 18 eyes (29.5%). Fixation stability correlated both with the disease stage and best-corrected visual acuity.

Conclusion: VMD is characterized by complex microperimetric abnormalities, involving the whole macular area. Microperimetry may contribute to the global clinical assessment of patients affected by VMD and could be used in future therapeutic approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0000000000001600DOI Listing
April 2018

Proangiogenic characteristics of activated macrophages from patients with age-related macular degeneration.

Neurobiol Aging 2017 03 10;51:71-82. Epub 2016 Dec 10.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel. Electronic address:

Macrophages were previously implicated in the pathogenesis of neovascular age-related macular degeneration (nvAMD). It is unclear if a specific macrophage phenotype is associated with nvAMD, and if macrophages from nvAMD patients are more pathogenic as compared with controls. To address these issues, we evaluated macrophages derived from peripheral blood monocytes of nvAMD patients and age-matched controls. Macrophages were assessed in terms of their expression profile and of their angiogenic potential in the choroid sprouting assay and the rat model of laser-induced choroidal neovascularization. Results showed a proangiogenic and inflammatory gene and protein expression profiles in classic (M[IFNγ and LPS]) and alternative (M[IL-4 and IL-13]) polarized macrophages. Furthermore, activated macrophages, particularly of the M(IFNγ and LPS) phenotype from nvAMD patients, were proangiogenic ex vivo and in vivo. These findings implicate activated human macrophages, particularly M(IFNγ and LPS) macrophages from nvAMD patients, in nvAMD. Further research is required to determine whether activated macrophages can serve as therapeutic targets in nvAMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2016.11.018DOI Listing
March 2017

Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration.

Sci Rep 2016 07 4;6:29046. Epub 2016 Jul 4.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Mononuclear phagocytes (MPs), including monocytes/macrophages, play complex roles in age-related macular degeneration (AMD) pathogenesis. We reported altered gene-expression signature in peripheral blood mononuclear cells from AMD patients, and a chemokine receptor signature on AMD monocytes. To obtain comprehensive understanding of MP involvement, particularly in peripheral circulation in AMD, we performed global gene expression analysis in monocytes. We separated monocytes from treatment-naïve neovascular AMD (nvAMD) patients (n = 14) and age-matched controls (n = 15), and performed microarray and bioinformatics analysis. Quantitative real-time PCR was performed on other sets of nvAMD (n = 25), atrophic AMD (n = 21), and controls (n = 28) for validation. This validated microarray genes (like TMEM176A/B and FOSB) tested, including differences between nvAMD and atrophic AMD. We identified 2,165 differentially-expressed genes (P < 0.05), including 79 genes with log2 fold change ≥1.5 between nvAMD and controls. Functional annotation using DAVID and TANGO demonstrated immune response alterations in AMD monocytes (FDR-P <0.05), validated by randomized data comparison (P < 0.0001). GSEA, ISMARA, and MEME analysis found immune enrichment and specific involved microRNAs. Enrichment of differentially-expressed genes in monocytes was found in retina via SAGE data-mining. These genes were enriched in non-classical vs. classical monocyte subsets (P < 0.05). Therefore, global gene expression analysis in AMD monocytes reveals an altered immune-related signature, further implicating systemic MP activation in AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep29046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931446PMC
July 2016
-->