OBJECTIVE: To demonstrate the therapeutic similarity of CT-P42 compared with reference aflibercept (Eylea) in adult patients with diabetic macular edema (DME). DESIGN: Randomized, active-controlled, double-masked, phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus with DME involving the center of the macula. METHODS: Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 ml) by intravitreal injection every 4 weeks (5 doses), then every 8 weeks (4 doses), in the main study period. Results up to week 24 are reported herein. MAIN OUTCOME MEASURES: The primary end point was mean change from baseline at week 8 in best-corrected visual acuity (BCVA) using the ETDRS chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the 2-sided 95% confidence interval (CI) (global assumptions) and 2-sided 90% CI (United States Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set. RESULTS: Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). Best-corrected visual acuity improved from baseline to week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the predefined equivalence margin of ±3 letters (95% CI, -0.73 to 1.88 [global]; 90% CI, -0.52 to 1.67 [FDA]). Through week 24, other efficacy results for the 2 groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing ≥1 treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups. CONCLUSIONS: This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 ml) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
- MeSH
- Biosimilar Pharmaceuticals administration & dosage MeSH
- Time Factors MeSH
- Diabetic Retinopathy * drug therapy diagnosis complications MeSH
- Double-Blind Method MeSH
- Angiogenesis Inhibitors * administration & dosage MeSH
- Intravitreal Injections MeSH
- Middle Aged MeSH
- Humans MeSH
- Macula Lutea pathology diagnostic imaging MeSH
- Macular Edema * drug therapy diagnosis etiology MeSH
- Follow-Up Studies MeSH
- Tomography, Optical Coherence methods MeSH
- Receptors, Vascular Endothelial Growth Factor * administration & dosage antagonists & inhibitors MeSH
- Recombinant Fusion Proteins administration & dosage MeSH
- Aged MeSH
- Vascular Endothelial Growth Factor A antagonists & inhibitors MeSH
- Treatment Outcome MeSH
- Dose-Response Relationship, Drug MeSH
- Visual Acuity MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- MeSH
- Humans MeSH
- Macula Lutea diagnostic imaging pathology MeSH
- Neuromyelitis Optica * diagnostic imaging pathology MeSH
- Tomography, Optical Coherence * MeSH
- Retina diagnostic imaging pathology MeSH
- Optic Neuritis diagnostic imaging pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
PURPOSE: To assess the intraday repeatability of macular architecture measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography (SD-OCT) and to evaluate the independence from intraindividual intraocular pressure (IOP) fluctuations. METHODS: In this single-center, time-point comparison study, 88 eyes with glaucoma, 53 eyes with ocular hypertension (OHT), and 253 healthy eyes underwent two standardized SD-OCT and intraocular pressure (IOP) measurements on the same day with a 5-h time gap. Bland-Altman plots, intraclass correlation coefficients (ICC), and random-effects model were used to analyze repeatability of entire retinal thickness, retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, and inner nuclear layer measurements. RESULTS: Intraday measurements were highly reproducible in all 3 groups. ICC were greater than 0.90, respectively. The pairwise comparisons of morphometric parameters showed a statistically significant difference (P < 0.001, respectively) between groups (glaucoma vs. control, glaucoma vs. OHT) and a significant influence of time points. No correlation was found between IOP fluctuations and morphometric parameters (P > 0.05, respectively), except for a weak positive correlation with GCL (rho = 0.109, P = 0.031). CONCLUSIONS: The evaluation of macular morphometric parameters of SD-OCT showed a high intraday repeatability and an excellent degree of agreement in glaucoma, ocular hypertension, and healthy groups. The fixed effects of time points were statistically significant. Except for a weak positive correlation of ganglion cell layer, variability did not appear to be affected by intraday IOP changes. Additional research is required to fully understand the impact of IOP fluctuations on macular morphometric parameters, considering the small observed IOP changes.
- MeSH
- Adult MeSH
- Glaucoma * diagnosis physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Macula Lutea * pathology diagnostic imaging MeSH
- Follow-Up Studies MeSH
- Nerve Fibers * pathology MeSH
- Intraocular Pressure * physiology MeSH
- Ocular Hypertension diagnosis physiopathology MeSH
- Tomography, Optical Coherence * methods MeSH
- Reproducibility of Results MeSH
- Retinal Ganglion Cells * pathology MeSH
- Aged MeSH
- Tonometry, Ocular MeSH
- Visual Fields physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
BACKGROUND AND AIMS: The aim of this study was to evaluate changes in vascular density in the macula after pars plana vitrectomy for idiopathic macular hole (IMD) with macular peeling and flap. METHODS: A prospective study of 35 eyes in 34 patients who had undergone standard surgery. Evaluated parameters were best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CRT), macular volume (TMV) and vascular density of the superficial and deep capillary plexus. The follow-up period was one year. RESULTS: We divided the total group into two: temporal and circular flap and total group. We compared the values after surgery with the preoperative values. In the total group, BCVA increased from 48.38 to 71.44 letters (P≤0.05). IOP changed from 15.24 to 14.76 mmHg (P>0.05). CRT decreased from 432.27 to 323.64 μm (P≤0.05). TMV changed from 0.26 to 0.25 mm3 (P>0.05). The vascular density of the superficial plexus decreased from 32 to 28% (P≤0.05). The intercapillary space of the superficial plexus increased from 68 to 72% (P≤0.05). The vascular density of the deep plexus increased from 17 to 23%. The intercapillary space of the deep vascular plexus decreased from 83 to 77%. Changes in vascular density and intercapillary space of the deep plexus were statistically significant for certain months after operations (P≤0.05). There were no significant differences between subgroups. CONCLUSION: The superficial plexus vascular density is almost the same in the temporal flap and in the foveal-sparing flap is decreased, and the deep plexus vascular density increased statistically significantly during the follow-up period after surgery.
- MeSH
- Surgical Flaps * blood supply MeSH
- Middle Aged MeSH
- Humans MeSH
- Macula Lutea * blood supply MeSH
- Microvascular Density MeSH
- Intraocular Pressure physiology MeSH
- Tomography, Optical Coherence MeSH
- Retinal Perforations * surgery MeSH
- Prospective Studies MeSH
- Retinal Vessels MeSH
- Aged MeSH
- Vitrectomy * methods MeSH
- Visual Acuity * MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The authors present a case study which describes the development of bilateral optic neuropathy as a complication of allogeneic hematopoietic stem cell transplantation (HSCT) in a patient who underwent a transplant for B-cell acute lymphoblastic leukemia (B-ALL). The patient, who was in remission with regard to the underlying hematological disease, developed edema of both optic discs and maculas three months after transplantation. The morphological finding regressed after treatment with corticoids and comprehensive systemic anti-infective therapy. However, the loss of function was not entirely restored. CASE REPORT: One year after the healing, the atrophy of the optic discs persisted, with corresponding findings in vessel density (VD), retinal nerve fibre layer (RNFL) and visual field changes. Electrophysiological examination by pattern electroretinogram (PERG) showed an alteration in retinal ganglion cells in the left eye, but with significant damage to nerve fibres on both sides. Visual evoked potential (VEP) verified bilateral non-inflammatory neurogenic lesions. This finding was also confirmed by functional magnetic resonance imaging (fMRI). Examination by structural magnetic resonance imaging (MRI) showed inflammatory changes in the optic nerve sheaths over time and a consequent marked narrowing of them. CONCLUSION: The authors believe that edema of the optic discs and maculas was caused by a combination of several factors. Firstly, MRI showed inflammatory changes in the optic nerve sheaths, which led to a blockade of axoplasmic transport. Another factor that may have played a part in the outcome was endothelial damage to blood vessels with impaired microcirculation supplying the optic nerve fibres, which contributed to the occurrence of macular edema.
Aims: To introduce a case report and review the literature on trauma-related acute macular neuroretinopathy as an unusual etiology of acute macular neuroretinopathy. Material and Methods: A 24-year-old man presented with unilateral paracentral scotoma following non-ocular trauma in a car accident. The relative afferent pupillary defect was negative and the best corrected visual acuities of both eyes were 10/10 (by the Snellen chart scale). Results: Retinoscopy revealed a reduced foveal reflex, along with a small pre-retinal hemorrhage over the mid-pathway of the supranasal arteriole. OCT images showed an obvious ellipsoid zone (EZ) layer disruption in the macula of the left eye. The infrared fundus photograph of the same eye revealed a distinct hyporeflective area involving the macula. On fundus angiography, no macular vascular lesion was detected. The scotoma persisted after 3 months follow-up. Conclusion: Non-ocular trauma including head or chest trauma without direct ocular injury accounts for most cases of trauma-related acute macular neuroretinopathy. It is important to distinguish this entity, given that there are also unremarkable findings in the retinal examination of these patients. Indeed, proper clinical suspicion leads to further suitable investigations and impedes other extraordinary images, which are the basic rules in the management of traumatic patients suffering multiple injuries and incurring medical expenses.
- MeSH
- Accidents, Traffic MeSH
- Fluorescein Angiography methods MeSH
- Humans MeSH
- Macula Lutea pathology MeSH
- Young Adult MeSH
- Tomography, Optical Coherence methods MeSH
- Wounds and Injuries complications MeSH
- Retinal Hemorrhage etiology MeSH
- Scotoma etiology complications MeSH
- White Dot Syndromes * diagnosis etiology MeSH
- Check Tag
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
AIM: The objective of this study was to evaluate the efficacy of diabetic macular edema (DME) therapy using subthreshold micropulse laser (SMPL) with a wavelength of 577 nm during a long-term monitoring period of 5 years. METHODS: The cohort included the total number of 52 eyes of 34 patients with DME. All underwent the standard laser treatment for the diabetic retinopathy outside the macula and DME treatment with SMPL. Subsequent check-ups were followed every 3 months in the first year of treatment, and every 4 to 6 months in the following years. The treatment was combined neither with focal macular laser nor with anti-VEGF therapy. RESULTS: The mean central retinal thickness (CRT) was 345.9 μm SD 122.6 μm at the beginning of the monitoring. At the end of the follow-up period five years after treatment it was 256.4 μm SD 98.4 μm. The mean CRT decreased by 89.5 μm SD 153.6 μm during 5 years. At the beginning of the monitoring, before treatment with SMPL, the best corrected visual acuity (BCVA) was 70.0, SD 10.1 ETDRS letters. One year after therapy, BCVA was 72, SD 10.0 letters, two years later it was 71.4, SD 10.4 letters and decreased to 66.9, SD 12.1 letters after 5 years. The mean BCVA decreased by merely 3.1, SD 10.9 letters during 5 years. CONCLUSION: Based on our long-term observations, the DME treatment with SMPL appears to be an effective method for reducing DME and protecting BCVA against rapid worsening.
- MeSH
- Diabetes Mellitus * therapy MeSH
- Diabetic Retinopathy * surgery MeSH
- Laser Coagulation methods MeSH
- Lasers MeSH
- Humans MeSH
- Macula Lutea * surgery MeSH
- Macular Edema * surgery MeSH
- Tomography, Optical Coherence MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Choroid blood supply MeSH
- Fovea Centralis anatomy & histology MeSH
- Glymphatic System physiology MeSH
- Blood-Retinal Barrier anatomy & histology physiology MeSH
- Humans MeSH
- Retina * anatomy & histology diagnostic imaging MeSH
- Retinal Vessels anatomy & histology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Bruch Membrane pathology MeSH
- Phagocytosis MeSH
- Humans MeSH
- Lipofuscin biosynthesis physiology adverse effects MeSH
- Macula Lutea * pathology MeSH
- Macular Degeneration * immunology physiopathology pathology MeSH
- Choroidal Neovascularization physiopathology MeSH
- Oxidative Stress physiology MeSH
- Cell Proliferation physiology MeSH
- Retinal Drusen pathology MeSH
- Retinal Pigment Epithelium cytology pathology MeSH
- Aging physiology MeSH
- Age Factors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
The adverse impact of adjacent contours on letter visual acuity is known as crowding but there is conflicting evidence that foveal crowding may be reduced or disappears under low contrast conditions. Potential differences in foveal crowding with contrast on clinical measurements of visual acuity, including test-retest repeatability, were assessed. Visual acuity was measured at the fovea on adult participants with normal vision under three different contrast levels (- 90, - 10 and - 5%). Three rows of 5 letters, each row differing in size by 0.05 logarithm of the minimum angle of resolution (logMAR) from largest to smallest were displayed at the center of a monitor. Crowding was varied by varying the separation between horizontally adjacent letters from 100% optotype size to 50%, 20% and 10% optotype size. Inter-row spacing was proportional to optotype size. Observers read the letters on the middle row only. Measurements continued by reducing the size of the letters until 3 or more errors were made and were repeated on two separate days. Visual acuity worsened as both letter contrast decreased and inter-optotype separation reduced (expressed as a percentage of letter width). When expressed in minutes of arc of separation the impact of crowding was the same across all contrasts. Crowding occurs for both high and low contrast charts and should be considered when assessing low contrast visual acuity. Test-retest repeatability showed little or no dependence on either contrast or inter-optotype separation.
- MeSH
- Adult MeSH
- Fovea Centralis * MeSH
- Humans MeSH
- Visual Acuity MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
