ABSTRACT
PURPOSE: To model and analyse the ocular biometry of new-born infants. METHODS: This work is based on previously published data of a cohort of 66 new-born infants aged 0-3 days. After exclusion of seven myopic subjects, the available retinoscopy, keratometry and ultrasound biometry data were analysed, along with calculated parameters such as lens power and whole eye power. RESULTS: Male infants have significantly flatter corneas that female infants (Mann-Whitney U test, p < 0.001), which was associated with a difference in gestational age between genders (multiple linear regression; p = 0.043). No other gender-based differences were seen. Corneal curvature (Pearson, r = 0.575; p < 0.001), lens power (r = -0.681; p < 0.001), and anterior chamber depth (r = 0.654; p < 0.001) were all correlated to axial length, but not refraction (r = -0.114; p = 0.42). Most ocular parameters were associated with gestational age (linear regression analysis; p < 0.05), rather than birth length, birth weight, fertilization method or parental myopia (all p > 0.05), suggesting scaled eye growth during the last weeks before birth. Multivariate Gaussian analysis demonstrated that a statistical eye model can be defined that generates synthetic data that is significantly equal to the original data (non-parametric Mann-Whitney test for equality; all p < 0.05), with similar variability (non-parametric Levene test; all p > 0.05). CONCLUSION: The eye undergoes a scaled growth until birth, at which time male and female infants have similar values. The models presented may serve as an early biometry reference.
Subject(s)
Axial Length, Eye/anatomy & histology , Biometry/methods , Lens, Crystalline/anatomy & histology , Refraction, Ocular/physiology , Female , Gestational Age , Humans , Infant, Newborn , MaleABSTRACT
PURPOSE: To investigate the response to intravitreal ranibizumab after failure of intravitreal bevacizumab in patients with diabetic macular edema (DME). METHODS: Demographics, visual acuity (VA), central macular thickness (CMT), and HbA1C were retrospectively collected from DME patients treated with second-line intravitreal ranibizumab at a tertiary hospital in 2012-2013 and followed for at least 3 months. RESULTS: Twenty-two patients (26 eyes) were included in the study, with a mean (±SD) age of 66 ± 8.1 years and followed for an average of 28.36 months. The mean number of intravitreal bevacizumab injections was 7.3 ± 2.8, and of intravitreal ranibizumab injections 5.11 ± 2.4. After 3 ranibizumab injections, 57% of eyes showed improvement in VA. The change in VA was statistically significant (p = 0.044) in those eyes where the pretreatment acuity for the second-line therapy was <20/40 (logMAR 0.3). CMT decreased from 435.95 ± 83.28 to 373.69 ± 44.39 µm (p = 0.01). The number of ranibizumab injections was significantly correlated with the change in CMT (p = 0.037). CONCLUSION: Intravitreal treatment with ranibizumab can be efficacious in eyes with DME that have failed to respond to bevacizumab.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Ranibizumab/therapeutic use , Aged , Female , Glycated Hemoglobin/metabolism , Humans , Intravitreal Injections , Male , Middle Aged , Retrospective Studies , Treatment Failure , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/drug effects , Visual Acuity/physiologyABSTRACT
PURPOSE: The European Society of Cataract & Refractive Surgeons (ESCRS) study reported a decrease in endophthalmitis rates from 0.34 % to 0.08 % with the use of intracameral cefuroxime. The purpose of this study was to compare the endophthalmitis rates before and after the introduction of intracameral cefuroxime (ICC) routinely at the end of cataract surgery. METHODS: A retrospective consecutive cohort study. We compared the rates of endophthalmitis between the years 2000-2006, and the years 2007-2014, after the pivotal publication of the ESCRS. Data collected included age, gender, culture results, initial and final visual acuity, and complications. Only patients that presented with endophthalmitis following cataract surgery performed at the two centers were included. RESULTS: Twenty-two cases of endophthalmitis occurred between the years 2000 and 2006, out of 26,663 cataract operations performed at the two centers, a rate of 0.083 %. Ten cases occurred between the years 2007 and 2014 out of 29,431 cataract operations, a rate of 0.034 %. The difference was statistically significant (p = 0.03) CONCLUSIONS: The introduction of prophylactic use of intracameral cefuroxime was associated with a significant reduction in post-operative endophthalmitis rates in our centers. We strongly recommend adoption of this routine by for all cataract operations except when contraindicated.
Subject(s)
Anterior Chamber/drug effects , Anti-Bacterial Agents/therapeutic use , Cataract Extraction/adverse effects , Cefuroxime/therapeutic use , Endophthalmitis/epidemiology , Eye Infections, Bacterial/epidemiology , Postoperative Complications , Adult , Aged , Aged, 80 and over , Bacteria/isolation & purification , Endophthalmitis/microbiology , Endophthalmitis/prevention & control , Eye Infections, Bacterial/microbiology , Eye Infections, Bacterial/prevention & control , Female , Humans , Incidence , Israel/epidemiology , Male , Middle Aged , Retrospective StudiesABSTRACT
Recent studies have provided strong evidence for a regulatory link among chromatin structure, histone modification, and splicing regulation. However, it is largely unknown how local histone modification patterns surrounding alternative exons are connected to differential alternative splicing outcomes. Here we show that splicing regulator Hu proteins can induce local histone hyperacetylation by association with their target sequences on the pre-mRNA surrounding alternative exons of two different genes. In both primary and mouse embryonic stem cell-derived neurons, histone hyperacetylation leads to an increased local transcriptional elongation rate and decreased inclusion of these exons. Furthermore, we demonstrate that Hu proteins interact with histone deacetylase 2 and inhibit its deacetylation activity. We propose that splicing regulators may actively modulate chromatin structure when recruited to their target RNA sequences cotranscriptionally. This "reaching back" interaction with chromatin provides a means to ensure accurate and efficient regulation of alternative splicing.
Subject(s)
Alternative Splicing/physiology , Chromatin/metabolism , ELAV Proteins/metabolism , Histones/metabolism , Neurons/metabolism , RNA Precursors/metabolism , Acetylation , Animals , Cells, Cultured , Exons/physiology , Histone Deacetylase 2/metabolism , Mice , Neurons/cytology , Transcription, Genetic/physiologyABSTRACT
Retinoic acid (RA) regulates gene transcription by activating the nuclear receptors retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPAR) ß/δ and their respective cognate lipid-binding proteins CRABP-II and FABP5. RA induces neuronal differentiation, but the contributions of the two transcriptional pathways of the hormone to the process are unknown. Here, we show that the RA-induced commitment of P19 stem cells to neuronal progenitors is mediated by the CRABP-II/RAR path and that the FABP5/PPARß/δ path can inhibit the process through induction of the RAR repressors SIRT1 and Ajuba. In contrast with its inhibitory activity in the early steps of neurogenesis, the FABP5/PPARß/δ path promotes differentiation of neuronal progenitors to mature neurons, an activity mediated in part by the PPARß/δ target gene PDK1. Hence, RA-induced neuronal differentiation is mediated through RAR in the early stages and through PPARß/δ in the late stages of the process. The switch in RA signaling is accomplished by a transient up-regulation of RARß concomitantly with a transient increase in the CRABP-II/FABP5 ratio at early stages of differentiation. In accordance with these conclusions, hippocampi of FABP5-null mice display excess accumulation of neuronal progenitor cells and a deficit in mature neurons versus wild-type animals.
Subject(s)
Antineoplastic Agents/pharmacology , Hippocampus/metabolism , Nerve Tissue Proteins/metabolism , Neural Stem Cells/metabolism , Neurogenesis/drug effects , Neurons/metabolism , PPAR-beta/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Retinoic Acid/metabolism , Signal Transduction/drug effects , Tretinoin/pharmacology , Animals , Cell Line , Fatty Acid-Binding Proteins/genetics , Fatty Acid-Binding Proteins/metabolism , Hippocampus/cytology , LIM Domain Proteins/genetics , LIM Domain Proteins/metabolism , Mice , Mice, Mutant Strains , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Nerve Tissue Proteins/genetics , Neural Stem Cells/cytology , Neurogenesis/physiology , Neurons/cytology , PPAR-beta/genetics , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Retinoic Acid/genetics , Signal Transduction/physiology , Sirtuin 1/genetics , Sirtuin 1/metabolismABSTRACT
OBJECTIVE: To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). DESIGN: Twenty-four-month, open-label, multicenter, phase IV extension study. PARTICIPANTS: Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. METHODS: Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). MAIN OUTCOME MEASURES: Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. RESULTS: Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. CONCLUSIONS: The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Wet Macular Degeneration/drug therapy , Aged , Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Cataract/chemically induced , Double-Blind Method , Female , Follow-Up Studies , Humans , Intraocular Pressure/drug effects , Intravitreal Injections , Male , Ocular Hypertension/chemically induced , Prospective Studies , Ranibizumab , Retinal Hemorrhage/chemically induced , Visual Acuity/drug effects , Visual Acuity/physiology , Wet Macular Degeneration/physiopathologyABSTRACT
PURPOSE: To investigate the effect of intravitreal bevacizumab on the visual and anatomic outcome of patients with exudative age-related macular degeneration presenting with good visual acuity (VA). METHODS: A file review was performed for all consecutive patients with newly diagnosed exudative age-related macular degeneration and initial VA of ≥ 20/40 treated in 2005 to 2010 and followed for at least 6 months. Treatment consisted of 3 loading doses of intravitreal bevacizumab every 6 weeks and was repeated when fluid or hemorrhage was present. RESULTS: The cohort included 130 patients (150 eyes). Mean follow-up was 20.2 ± 13.2 months, and mean number of injections was 11.3 ± 6.2. At the last examination, VA was stable or improved in 106 eyes (70.7%); 11 eyes (7.3%) lost ≥ 3 lines. Mean logarithm of the minimum angle of resolution VA measured 0.22 ± 0.1 (0-0.3) at presentation and 0.22 ± 0.2 (0-1.3) at the last visit. Corresponding values for central macular thickness were 267 ± 75 µm (137-562) and 226 ± 75 µm (75-568) (P = 0.14). The most frequent complication (18 eyes, 12%) was corneal epithelial defects. CONCLUSION: Prompt intravitreal bevacizumab treatment for newly diagnosed exudative age-related macular degeneration in patients with good initial best-corrected visual acuity is associated with sustained or improved vision and a good safety profile. Attempts should be made to expedite the access of these patients to treatment, regardless of initial VA.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Visual Acuity/physiology , Wet Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Bevacizumab , Exudates and Transudates , Female , Follow-Up Studies , Humans , Intraocular Pressure/drug effects , Intravitreal Injections , Male , Middle Aged , Retina/pathology , Retreatment , Retrospective Studies , Tonometry, Ocular , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Wet Macular Degeneration/physiopathologyABSTRACT
BACKGROUND: To investigate the role of inflammation in age-related macular degeneration by measuring the levels of cytokines in the aqueous humour. METHODS: Samples of aqueous humour were collected from 34 patients with age-related macular degeneration and 16 age-matched control subjects undergoing cataract surgery. Age-related macular degeneration stage was determined clinically, before surgery. Levels of cytokines were measured using Luminex X-MAP technology, and positive results were verified by Western blot. RESULTS: Age-related macular degeneration was moderate in 18 patients and advanced in 16. The advanced age-related macular degeneration group was further divided into patients with active choroidal neovascularization (n = 7), disciform scar (n = 7) or central geographic atrophy (n = 2). Higher-than-normal levels of monocyte chemoattractant protein-1 in the aqueous humour were associated with advanced age-related macular degeneration (200 ± 140 pg/mL vs. 100 ± 61 pg/mL; P = 0.03), especially active choroidal neovascularization (255 ± 155 pg/mL; P = 0.02), Western blot analysis verified the monocyte chemoattractant protein-1 findings. Patients with disciform scar showed a trend of abnormally high levels of interleukin-12 (p70) (1.7 ± 2.4 pg/mL vs. 0.2 ± 1 pg/mL; P = 0.07), tumour necrosis factor-α (1.8 ± 2.4 pg/mL vs. 0.3 ± 1 pg/mL; P = 0.06) and interleukin-12 (4.7 ± 6.4 pg/mL vs. 1.2 ± 2.1 pg/mL; P = 0.08). CONCLUSION: Elevated levels of inflammation-related cytokines in the aqueous humour in various stages of age-related macular degeneration may suggest a pathogenic role of inflammation. Monocyte chemoattractant protein-1 may be indicative of the angiogenic phase. Further corroborative studies are required.
Subject(s)
Aqueous Humor/metabolism , Chemokine CCL2/metabolism , Macular Degeneration/metabolism , Aged , Aged, 80 and over , Blotting, Western , Cataract Extraction , Female , Humans , Immunoassay/methods , MaleABSTRACT
Purpose: To compare intra- and postoperative complications in combined phacoemulsification and pars plana vitrectomy surgeries performed in patients with non-proliferative diabetic retinopathy (NPDR) vs. proliferative diabetic retinopathy (PDR). Methods: Retrospective, case series of patients with diabetic retinopathy who underwent combined phacovitrectomy surgery between 2008 and 2017. We compared intraoperative complications including posterior capsular rupture and retinal tear, and postoperative complications including corneal edema, macular edema (ME), epiretinal membrane (ERM), neovascular glaucoma and persistent inflammation. Results: A total of 104 eyes of 104 patients were included in this study. Twenty-four eyes (23.1%) were categorized as NPDR and 80 eyes (76.9%) as PDR. The most common indications for surgery in the NPDR group were ERM (67%) and rhegmatogenous retinal detachment (12.5%), while in the PDR group, indications were vitreous hemorrhage (56%) and tractional retinal detachment (19%). The most common intraoperative complication was retinal tear (8% in NPDR and 19% in PDR, p = 0.195) and postoperative complication was ME (29% in NPDR and 26% in PDR, p = 0.778). There were no statistically significant differences in intra- and postoperative complication rates between the NPDR and PDR groups, even after adjusting for confounders; patient age at surgery and indication for surgery. Conclusion: After combined phacovitrectomy in NPDR and PDR patients, new-onset ME was found in about a quarter of eyes in both groups. Intraoperative anti-VEGF or steroid administration, and intense postoperative anti-inflammatory medication and follow-up should be regarded after phacovitrectomy regardless of the DR level.
ABSTRACT
BACKGROUND AND OBJECTIVE: To assess the foveal microvascular structure of children with retinopathy of prematurity (ROP) treated with diode laser photocoagulation using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: OCTA was performed at a tertiary medical center in 17 children (27 eyes) aged 4 to 16 years with a history of diode laser photocoagulation treated ROP. OCTA parameters were compared with those of 12 healthy age-matched controls (23 eyes) attending the orthoptics clinic and correlated with clinical factors. RESULTS: Compared with controls, the ROP group had a smaller foveal avascular zone area (P < .001), lower deep vascular plexus density (P < .001), lower flow density (P = .025), and greater central macular thickness (P < .001). High intraventricular hemorrhage grade correlated with smaller foveal avascular zone area (P = .008) and greater inner macular thickness (P = .047). There was no impact of gestational age, birth weight, or refractive status. CONCLUSION: OCTA can identify significant quantifiable long-term macular microvascular and structural changes in this patient population. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):194-201.].
Subject(s)
Retinopathy of Prematurity , Tomography, Optical Coherence , Child , Fluorescein Angiography/methods , Fovea Centralis/blood supply , Humans , Infant , Infant, Newborn , Retinal Vessels , Retinopathy of Prematurity/diagnosis , Retinopathy of Prematurity/surgery , Tomography, Optical Coherence/methods , Visual AcuityABSTRACT
OBJECTIVE: To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: A 12-month, multicenter, randomized, double-masked, active-controlled, phase IIIb study. PARTICIPANTS: Patients with primary or recurrent subfoveal CNV secondary to AMD (353 patients), with predominantly classic, minimally classic, or occult (no classic component) lesions. INTERVENTION: Patients were randomized (1:1:1) to 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection). MAIN OUTCOME MEASURES: Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 12 and the incidence of adverse events (AEs). RESULTS: In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 µm in 0.3 mg quarterly, -105.6 µm in 0.5 mg quarterly, and -105.3 µm in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups; 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups; 20.9%, monthly group). There were 9 ocular serious AEs and 3 deaths; 1 death was suspected to be study related (cerebral hemorrhage; 0.5 mg quarterly group). The incidences of key arteriothromboembolic events were low. CONCLUSIONS: After 3 initial monthly ranibizumab injections, both monthly (0.3 mg) and quarterly (0.3 mg/0.5 mg) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD. At month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens. The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The safety profile was similar to that reported in prior ranibizumab studies.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal/administration & dosage , Choroidal Neovascularization/drug therapy , Macular Degeneration/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/physiopathology , Double-Blind Method , Drug Administration Schedule , Female , Fluorescein Angiography , Humans , Intravitreal Injections , Macular Degeneration/diagnosis , Macular Degeneration/physiopathology , Male , Middle Aged , Ranibizumab , Retina/pathology , Tomography, Optical Coherence , Treatment Outcome , Visual Acuity/physiologyABSTRACT
PURPOSE: To investigate the benefit of intravitreal bevacizumab as supplemental or primary treatment for retinopathy of prematurity. METHODS: The files of nine consecutive infants treated with intravitreal bevacizumab for bilateral severe posterior retinopathy of prematurity were reviewed. RESULTS: Gestational age was 24 weeks to 27 weeks, and birth weight was 660 g to 1,131 g. Indications for treatment were retinopathy of prematurity progression from Stage 3 to 4A or 2 to 3 with extraretinal neovascularization despite laser treatment; active neovascular Stage 4A disease after laser and cryo-treatment; anterior segment neovascularization and bleeding after laser treatment; and aggressive posterior disease with tunica vasculosa lentis and vitreous haze, which prevented laser treatment. One patient (two eyes) underwent lens-sparing vitrectomy after bevacizumab treatment; one eye acquired macular fold. One patient underwent bilateral scleral buckle. Bevacizumab treatment was associated with subsidence of the active vascular component in all eyes. Anatomical results were favorable in 17 eyes. There were no local or systemic complications. CONCLUSION: Intravitreal bevacizumab may serve as a supplemental therapeutic agent for severe laser-refractory retinopathy of prematurity or as monotherapy when media opacities preclude diode laser photocoagulation or the patient is too sick for lengthy laser treatment.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Retinal Neovascularization/drug therapy , Retinopathy of Prematurity/drug therapy , Bevacizumab , Birth Weight , Chemotherapy, Adjuvant , Female , Gestational Age , Humans , Infant, Extremely Low Birth Weight , Infant, Newborn , Intravitreal Injections , Male , Retinal Neovascularization/classification , Retinal Neovascularization/physiopathology , Retinopathy of Prematurity/classification , Retinopathy of Prematurity/physiopathology , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiologyABSTRACT
PURPOSE: There are 2 common alleles for Hp (Hp-1 and Hp-2) and 3 common Hp genotypes: Hp1-1, Hp2-1, and Hp2-2. The haptoglobin genotype may play a dual role in morbidities of diabetes: Hp1-1, protective and Hp2-2, provocative. This study investigated the possible association of haptoglobin genotypes with onset of retinopathy in Type 2 diabetes (DM2). METHODS: The sample included 98 consecutive adults with DM2 under routine outpatient follow-up from 2007 to 2009 who met the criteria for either no retinopathy at ≥10 years after diagnosis (Group 1) or proliferative retinopathy at ≤10 years after diagnosis (Group 2). Blood samples were collected for haptoglobin genotyping by polymerase chain reaction. Findings were compared between and within groups. RESULTS: Eighty-four patients had no retinopathy and 14 had early proliferative retinopathy. The distributions of the Hp genotypes were as follows: no-retinopathy group: 28.6% Hp1-1, 35.7% Hp2-1, and 35.7% Hp2-2 and proliferative retinopathy group: 22.6% Hp1-1, 27.4% Hp2-1, and 50% Hp2-2 (NS). On statistical analysis (limited to the larger no-retinopathy group), a predominance of Hp1-1 was noted in older patients; Hp2-2 was associated with an increased rate of stroke. CONCLUSION: The Hp genotype apparently plays no role in the development or worsening of proliferative retinopathy in DM2. Hp1-1 may be involved in delaying the onset of diabetes. Hp2-2 may pose a microvascular risk.
Subject(s)
Diabetes Mellitus, Type 2/diagnosis , Diabetic Retinopathy/genetics , Genotype , Haptoglobins/genetics , Adult , Aged , Aged, 80 and over , Diabetic Retinopathy/diagnosis , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Ophthalmoscopy , Polymerase Chain Reaction , Polymorphism, Genetic , Risk FactorsABSTRACT
Ocular complications after renal transplantation are common in adults. Nevertheless, data regarding these complications in children are insufficient. The purpose of the present study was to assess ocular morbidity in pediatric renal graft recipients. A retrospective observational study of 71 patients aged 11.2 +/- 5.5 yr was conducted. Mean duration of follow-up was 5.6 +/- 3.5 yr. A total of 16 ocular complications were found in 12 (17%) of the patients. Three patients suffered from more than one complication. Cataract was the most common finding (six patients, 8.4%) followed by swollen disk and hypertensive retinopathy in four patients (5.7%) each and increased intra-ocular pressure in two patients (3%). Mean time interval between transplantation and occurrence of first abnormal ocular finding was 37 +/- 34.5 months. The follow-up time was significantly longer in patients with ophthalmological problems than in those without complications (7.8 yr vs. 5.2 yr, p < 0.02). No statistically significant association was found between the occurrence of ocular complications and the age of the patients at transplantation, donor source, duration of dialysis prior to transplantation, previous corticosteroid therapy or presence of acute rejection episodes. The results of the study point to the importance of regular concurrent ophthalmological follow-up in pediatric renal graft recipients to reduce/prevent ocular morbidity.
Subject(s)
Cataract/etiology , Kidney Transplantation/adverse effects , Macular Edema/etiology , Ocular Hypertension/etiology , Retinal Diseases/etiology , Adolescent , Cataract/epidemiology , Child , Female , Follow-Up Studies , Humans , Israel/epidemiology , Kidney Failure, Chronic/surgery , Macular Edema/epidemiology , Male , Morbidity/trends , Ocular Hypertension/epidemiology , Prognosis , Retinal Diseases/epidemiology , Retrospective Studies , Risk Factors , Time FactorsABSTRACT
PURPOSE: The purpose of this study was to report our experience with intravitreal bevacizumab for inflammation-related choroidal neovascularization in two tertiary centers. METHODS: This study was a retrospective analysis of patients with choroidal neovascularization related to inflammatory diseases, treated with intravitreal bevacizumab injections (1.25 mg/0.05 mL). RESULTS: Ten eyes of 10 patients (range, 14-78 years; mean age, 44 years) with underlying uveitis were treated with intravitreal bevacizumab for inflammation-related choroidal neovascularization from 2006 to 2008. Mean follow-up time was 13 +/- 8 months, and the mean number of injections was 2.7 +/- 2. Resolved leakage on fluorescein angiography and resolution of subretinal fluid on optical coherence tomography occurred in all patients, with improvement in visual acuity in 9 of 10 eyes and no change in visual acuity in 1 of 10 eyes. Seven patients received additional treatment based on the underlying condition. Mean macular thickness on optical coherence tomography decreased from 394 +/- 116 microm to 254 +/- 52 microm (P < 0.01). Mean visual acuity improved from 0.87 +/- 0.74 logarithm of the minimum angle of resolution to 0.38 +/- 0.63 (P = 0.005). Seven patients reached a visual acuity of 0.2 logarithm of the minimum angle of resolution (Snellen 6/9) or better. CONCLUSION: Intravitreal bevacizumab is an effective treatment for choroidal neovascularization related to inflammatory diseases when inflammation is controlled.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal/administration & dosage , Choroidal Neovascularization/drug therapy , Uveitis/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Adolescent , Adult , Aged , Antibodies, Monoclonal, Humanized , Bevacizumab , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/physiopathology , Drug Therapy, Combination , Female , Fluorescein Angiography , Glucocorticoids/administration & dosage , Humans , Immunosuppressive Agents/administration & dosage , Injections , Male , Middle Aged , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Uveitis/diagnosis , Uveitis/physiopathology , Visual Acuity/physiology , Vitreous Body , Young AdultABSTRACT
We report our experience with photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) in young adult patients. This was a retrospective study of young adults with CNV treated with PDT. Data collected included age, diagnosis, type and size of CNV, number of treatments, visual outcome, and side effects. Ten patients (11 eyes) were included in the study (mean age 27.2 +/- 13.3 years). Etiologies included multifocal choroiditis (3 eyes), idiopathic CNV (5 eyes), central serous chorioretinopathy (1 eye), and toxoplasma (2 eye). The mean number of treatments was 2 +/- 0.7 and the mean follow-up time was 13.1 +/- 9.5 months. Initial visual acuity (VA) ranged from 20/25 to 20/1,200 (mean logMAR 0.6 +/- 0.5), and improved to 20/20 to 20/250 (mean logMAR 0.46 +/- 0.4) (P = 0.51). Of the four eyes that received additional treatment with oral steroids, one of which also received intravitreal bevacizumab (Avastin) injections, all had visual acuity improvement of 2 or more lines, while only two of seven eyes that received PDT alone showed such improvement. PDT can improve visual outcome in a subgroup of young patients with subfoveal CNV especially when supplemented with oral steroid and bevacizumab injections.
Subject(s)
Choroidal Neovascularization/drug therapy , Photochemotherapy , Administration, Oral , Adolescent , Adult , Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Bevacizumab , Central Serous Chorioretinopathy/complications , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/etiology , Choroidal Neovascularization/physiopathology , Choroiditis/complications , Female , Fluorescein Angiography , Humans , Male , Middle Aged , Retrospective Studies , Toxoplasmosis/complications , Treatment Outcome , Visual Acuity/drug effects , Young AdultABSTRACT
PURPOSE: To evaluate and correlate levels of various proteins involved in coagulation, inflammation and angiogenesis processes in the vitreous of patients with different vitreoretinal pathologies. METHODS: Vitreous samples were collected from patients scheduled for pars plana vitrectomy for the treatment of rhegmatogenous retinal detachment (RRD), vitreous haemorrhage or tractional retinal detachment associated with proliferative diabetic retinopathy (PDR). Macular hole and epiretinal membrane served as controls. Levels of vascular endothelial growth factor, thrombin-antithrombin III complex, interleukin-8, tissue factor, thrombomodulin, P-selectin, D-dimer and tissue factor pathway inhibitor were compared among the vitreoretinal pathology groups. RESULTS: Compared to controls, patients with PDR had significantly higher levels of thrombin-antithrombin III complex (p < 0.001), vascular endothelial growth factor (p < 0.001), D-dimer (p = 0.038) and interleukin-8 (p = 0.04), and patients with RRD group had significantly higher levels only of thrombin-antithrombin III complex (p < 0.001). There was a significant linear correlation between levels of P-selectin and D-dimer (p = 0.003), P-selectin and interleukin-8 (p < 0.001), and D-dimer and IL-8 (p = 0.007). These correlations were particularly strong in the PDR group compared to the other groups. CONCLUSION: Patients with PDR manifest high coagulative and angiogenic activity in the vitreous. These pathways are highly correlated with the inflammatory cascade.
ABSTRACT
PURPOSE: To assess the effect of adjunctive intravitreal bevacizumab treatment on neovascular glaucoma (NVG). METHODS: The medical records of all consecutive patients with NVG treated with intravitreal bevacizumab at our center from May 2006 to February 2008 were reviewed. The data collected included background features, findings on full ophthalmologic examination (including visual acuity, gonioscopy, and intraocular pressure), glaucoma medications prescribed, and additional procedures for glaucoma performed before and after bevacizumab injection.The interval between the diagnosis of NVG and intravitreal bevacizumab treatment was calculated. RESULTS: Eighteen patients (6 male, 12 female; mean age 63-/+13.2 years) met the study criteria. Causes of NVG were proliferative diabetic retinopathy (n=14), central retinal vein occlusion (n=2), occlusive vasculitis (n=1), and panuveitis (n=1). The mean duration of followup was 52 (-/+12) weeks. Mean intraocular pressure decreased from 32.3 (-/+4.99) to 18 (-/+6.1) mmHg (p<0.0001) and mean number of glaucoma medications decreased from 3.16 (-/+1.2) to 2.55 (-/+1.46) (p=0.1938). An interval of less than 6 months between the start of bevacizumab treatment and diagnosis was associated with better final visual acuity than delayed treatment (0.82-/+0.4 logMAR vs 1.88-/+1.1 logMAR, p=0.002) and a better regression of iris neovascularization (22% vs 89%; p=0.015). CONCLUSIONS: Intravitreal bevacizumab is beneficial for the treatment of anterior segment neovascularization and NVG when used as an adjunct, making the administration of additional treatment for the underlying cause possible. Bevacizumab should be instituted promptly after diagnosis, before irreversible anatomic and functional damage occurs.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Glaucoma, Neovascular/drug therapy , Angiogenesis Inhibitors/administration & dosage , Anterior Eye Segment/blood supply , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antihypertensive Agents/therapeutic use , Bevacizumab , Female , Glaucoma, Neovascular/etiology , Gonioscopy , Humans , Injections , Intraocular Pressure/drug effects , Male , Middle Aged , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity , Vitreous BodyABSTRACT
AIM: To determine the rate and possible contributors for post-pars plana vitrectomy (PPV) epiretinal membrane (ERM) in patients treated for rhegmatogenous retinal detachment (RRD). METHODS: This prospective, nonrandomized study comprised 47 consecutive patients (47 eyes) with acute RRD treated with 23 G post-PPV. All participants were followed prospectively for 6mo for the development of ERM using spectral domain optical coherence tomography. Preoperative and intraoperative data were collected by questionnaires to surgeons. Main outcome measure was the percentage of the ERM formation following post-PPV for RRD. RESULTS: ERM developed postoperatively in 23 eyes (48.9%), none necessitated surgical removal. There was a statistically significant difference between patients with and without ERM postoperatively in preoperative best corrected visual acuity (median logMAR 1.9 vs 0.3, respectively; P=0.003) rate of macula-off (69.6% vs 37.5%, respectively, P=0.028), and rate of ≥5 cryo-applications (55.6% and 18.8%, respectively, P=0.039). ERM developed mainly between the 1st and 3rd months of follow-up. Macula-off status increased the risk of ERM, with the odds ratio of 3.81 (P=0.031). CONCLUSION: ERM is a frequent post RRD finding, and its development is associated with macula-off RRD.
ABSTRACT
PURPOSE: The Tyr402His variant of complement factor H (CFH) is associated with age-related macular degeneration (AMD) in several populations. Our aim was to evaluate if this single nucleotide polymorphism (SNP) is associated with AMD in the Israeli population and see if it underlies heterogeneity in clinical manifestation and responses to photodynamic therapy (PDT), which characterize neovascular AMD (NVAMD). METHODS: Genotyping for the Tyr402His variant was performed in 240 NVAMD patients (78.1+/-7 age range) and 118 controls (70.8+/-8.2 age range). Genotyping was correlated with clinical characteristics and treatment parameters in sequential 131 NVAMD patients who underwent PDT. RESULTS: TheTyr402His coding allele was associated with NVAMD in the Israeli population: odds ratio (OR)=1.9; 95% confidence interval (CI)=1.3-2.6; p=0.0002. Homozygosity for this variant was associated with an OR of 3.4 (95% CI: 1.7-6.8) for having AMD. There was no association among this SNP and age of onset of NVAMD, gender, neovascular lesion size, initial or final visual acuity, and number of PDT sessions required. CONCLUSIONS: In accordance with findings from the majority of previous study populations, the Tyr402His variant of CFH is associated with NVAMD in Israel. However, heterogeneity in clinical manifestations of NVAMD and in its response to PDT is not underlined by this CFH variant and may be accounted for by other genetic and environmental factors.