-
1.
Long-term follow-up of chronic central serous chorioretinopathy after successful treatment with photodynamic therapy or micropulse laser.
van Rijssen, TJ, van Dijk, EHC, Scholz, P, Breukink, MB, Dijkman, G, Peters, PJH, Tsonaka, R, Keunen, JEE, MacLaren, RE, Hoyng, CB, et al
Acta ophthalmologica. 2021;(7):805-811
-
-
Free full text
-
Abstract
PURPOSE To describe the treatment outcomes and recurrence risk of chronic central serous chorioretinopathy (cCSC) in patients who had complete resolution of subretinal fluid (SRF) after either primary half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) in the PLACE trial. METHODS This multicentre prospective follow-up study evaluated cCSC patients at 1 year after completion of the PLACE trial. Outcomes included: complete resolution of SRF on OCT, best-corrected visual acuity (BCVA) in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, retinal sensitivity on microperimetry and a visual function questionnaire (NEI-VFQ25). RESULTS Twenty-nine out of 37 patients who received half-dose PDT and 15 out of 17 patients who received HSML could be evaluated at final visit. At final visit, 93% of the patients treated with half-dose PDT had complete resolution of SRF, compared with 53% of HSML-treated patients (p = 0.006). At final visit, the mean estimate increase in the PDT group compared with the HSML group was + 2.1 ETDRS letters, +0.15 dB for the retinal sensitivity and + 5.1 NEI-VFQ25 points (p = 0.103, p = 0.784 and p = 0.071, respectively). The mean estimated central retinal thickness in the half-dose PDT group was -7.0 µm compared with the HSML group (p = 0.566). The mean estimated subfoveal choroidal thickness in the half-dose PDT group was -16.6 µm compared with the HSML group (p = 0.359). CONCLUSION At 20 months after treatment, cCSC patients successfully treated with half-dose PDT are less likely to have recurrences of SRF compared with those successfully treated with HSML. However, functional outcomes did not differ.
-
2.
The Clinical Importance of Changes in Diabetic Retinopathy Severity Score.
Ip, MS, Zhang, J, Ehrlich, JS
Ophthalmology. 2017;(5):596-603
Abstract
PURPOSE To investigate the clinical importance of changes in diabetic retinopathy severity score (DRSS) in patients with diabetic macular edema (DME) treated with intravitreal ranibizumab. DESIGN Post hoc analysis of the phase III RIDE and RISE studies of ranibizumab for treatment of DME. PARTICIPANTS Four hundred sixty-eight eyes treated with ranibizumab from randomization with gradable DRSS on baseline fundus photographs. METHODS Visual and anatomic outcomes were examined in eyes grouped according to DRSS change from baseline to month 24. MAIN OUTCOME MEASURES Mean best-corrected visual acuity (BCVA) letter score change, proportion of patients with 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letter score change, mean contrast sensitivity change, proportion of patients with resolved macular edema, and leakage on fluorescein angiography. RESULTS Most (56.8%) patients treated with ranibizumab experienced 1-step or more improvement in DRSS from baseline to month 24; 40.0% had no change, and 3.2% experienced DRSS worsening. Patients with DRSS stability or improvement had greater mean BCVA letter score changes (+15.1, +14.2, +11.3, and +11.2 letters for ≥3-step improvement, ≥2-step improvement, 1-step improvement, and no DRSS change, respectively) compared with +5.0 letters in patients who had any DRSS worsening. Best-corrected visual acuity letter score gain of 15 letters or more was more common in patients with 2-step or 3-step or more DRSS improvement (51.9% and 44.6%, respectively) compared with those with a 1-step DRSS improvement, no change, or worsening (37.9%, 39.6%, and 26.7%, respectively). A loss of 15 letters or more in BCVA was more common in patients with any DRSS worsening (13.3%) compared with patients who had stable or improved DRSS (0%-2.8%). Resolution of macular edema was more common in patients with DRSS improvement: 84.2%, 87.7%, and 92.3% of patients with 1-step, 2-step or more, and 3-step or more improvement in DRSS achieved central foveal thickness of 250 μm or less, compared with 65.2% and 53.3% of patients who had no DRSS change or any DRSS worsening. CONCLUSIONS These findings provide further support that improvement in DRSS is a clinically important outcome that should be evaluated as a measure of treatment effectiveness in future studies of diabetic eye disease.
-
3.
X-Linked Retinoschisis in Juveniles: Follow-Up by Optical Coherence Tomography.
Hu, QR, Huang, LZ, Chen, XL, Xia, HK, Li, TQ, Li, XX
BioMed research international. 2017;:1704623
Abstract
Purpose. To explore the structural progression of X-linked retinoschisis (XLRS) in patients by using spectral-domain optical coherence tomography (SD-OCT). Design. Retrospective, observational study. Methods. Patients who were diagnosed with XLRS by genetic testing underwent comprehensive ophthalmological examinations from December 2014 to October 2016. Each eye was measured by SD-OCT using the same clinical protocol. A correlation between best-corrected visual acuity (VA) and SD-OCT measurements was observed. Results. Six patients demonstrated retinoschisis (12 eyes) and typical foveal cyst-like cavities (10 eyes) on SD-OCT images with a mean logMAR VA of 0.48. The median age was 7.5 years at the initial visit. Their foveal retinal thickness (516.9 μm) and choroid thickness (351.4 μm) decreased at a rate of 38.1 and 7.5 μm, respectively, at the 10.5-month follow-up visit; however, there were no significant differences (P = 0.622 and P = 0.406, resp.). There was no significant correlation between VA, the foveal retinal thickness, and subfoveal choroid thickness. Conclusions. SD-OCT images for XLRS patients during the juvenile period revealed no significant changes in the fundus structure, including the foveal retinal thickness and choroid thickness within one-year follow-up. There was a lack of correlation between VA, foveal retinal thickness, and subfoveal choroid thickness.
-
4.
The Role of the Human Visual Cortex in Assessment of the Long-Term Durability of Retinal Gene Therapy in Follow-on RPE65 Clinical Trial Patients.
Ashtari, M, Nikonova, ES, Marshall, KA, Young, GJ, Aravand, P, Pan, W, Ying, GS, Willett, AE, Mahmoudian, M, Maguire, AM, et al
Ophthalmology. 2017;(6):873-883
-
-
Free full text
-
Abstract
PURPOSE Gene therapy (GT) has offered immense hope to individuals who are visually impaired because of RPE65 mutations. Although GT has shown great success in clinical trials enrolling these individuals, evidence for stability and durability of this treatment over time is still unknown. Herein we explored the value of functional magnetic resonance imaging (fMRI) as an objective measure to assess independently the longevity of retinal GT. DESIGN Individuals with RPE65 mutations who underwent GT in their worse-seeing eye in a phase 1 clinical trial received a second subretinal injection in their contralateral eye in a follow-on clinical trial. Functional magnetic resonance imaging (MRI) was performed longitudinally to assess brain responses of patients with RPE65 mutations after stimulation of their most recently treated eye before and 1 to 3 years after GT. PARTICIPANTS Seven participants with RPE65 mutations who were part of the follow-on clinical trial gave informed consent to participate in a longitudinal neuroimaging fMRI study. METHODS All participants underwent fMRI using a 3-Tesla MRI system and a 32-channel head coil. Participants' cortical activations were assessed using a block design paradigm of contrast reversing checkerboard stimuli delivered using an MRI-compatible video system. MAIN OUTCOME MEASURES The primary parameters being measured in this study were the qualitative and quantitative fMRI cortical activations produced by our population in response to the visual task. RESULTS Functional MRI results showed minimal or no cortical responses before GT. Significant increase in cortical activation lasting at least 3 years after GT was observed for all participants. Repeated measures analysis showed significant associations between cortical activations and clinical measures such as full-field light sensitivity threshold for white, red, and blue colors; visual field; and pupillary light reflex. CONCLUSIONS Participants with RPE65 mutations showed intact visual pathways, which became responsive and strengthened after treatment. Functional MRI results independently revealed the efficacy and durability of a 1-time subretinal injection. The fMRI results paralleled those recently reported during the long-term clinical evaluations of the same patients. Results from this study demonstrated that fMRI may play an important role in providing complementary information to patients' ophthalmic clinical evaluation and has usefulness as an outcome measure for future retinal intervention studies.
-
5.
Visual and Anatomic Outcomes in Patients with Diabetic Macular Edema with Limited Initial Anatomic Response to Ranibizumab in RIDE and RISE.
Pieramici, DJ, Wang, PW, Ding, B, Gune, S
Ophthalmology. 2016;(6):1345-50
Abstract
PURPOSE To explore the visual acuity and anatomic outcomes over 24 months of patients with diabetic macular edema (DME) who showed a delayed anatomic response after 3 ranibizumab injections in the RIDE and RISE trials. DESIGN Analysis of data from RIDE and RISE, 2 phase III, parallel, randomized, multicenter, double-masked trials (ClinicalTrials.gov identifiers, NCT00473382 and NCT00473330). PARTICIPANTS Patients with DME (n = 681) who received monthly intravitreal ranibizumab 0.3-mg injections, ranibizumab 0.5-mg injections, or sham injections. METHODS Patients were separated into 3 groups: delayed responders (ranibizumab-treated patients with ≤10% central foveal thickness [CFT] reduction after 3 injections), immediate responders (ranibizumab-treated patients with >10% CFT reduction after 3 injections), and sham recipients. Central foveal thickness was measured by time-domain optical coherence tomography, best-corrected visual acuity (BCVA) was measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores, and diabetic retinopathy (DR) was measured by the standardized ETDRS severity scale (using fundus photographs). MAIN OUTCOME MEASURES Month-24 CFT, BCVA, and DR severity levels. RESULTS In RIDE and RISE, 9% to 10% of ranibizumab-treated eyes were delayed responders. At month 24, delayed responders had less CFT reduction (median, -102 μm) from baseline compared with immediate responders (median, -274 μm; P < 0.0001). Delayed responders gained a median of 10 letters at 24 months, similar to immediate responders (14 letters; P = 0.15). At month 24, DR improvement among the delayed responders (31% and 22% of patients with ≥2- or ≥3-step DR improvement, respectively) was comparable with that among immediate responders (42% and 17%, respectively; P = 0.21 and P = 0.48, respectively). CONCLUSIONS With continued treatment, at month 24, patients with DME with delayed anatomic response (≤10% CFT reduction) after 3 ranibizumab injections had visual acuity gains and DR improvement similar to those of patients with DME who had immediate anatomic response.
-
6.
Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase III trials.
Danis, RP, Sadda, S, Li, XY, Cui, H, Hashad, Y, Whitcup, SM
The British journal of ophthalmology. 2016;(6):796-801
-
-
Free full text
-
Abstract
BACKGROUND/AIM: To assess long-term effects of dexamethasone intravitreal implant (DEX implant) monotherapy on retinal morphology in diabetic macular oedema (DME). METHODS Two multicentre, masked, phase III studies with identical protocols randomised patients with DME, best-corrected visual acuity of 34-68 Early Treatment Diabetic Retinopathy Study letters and central subfield retinal thickness (CSRT) ≥300 µm to DEX implant 0.7, 0.35 mg or sham procedure. Patients were followed up for 3 years (39 months if treated at month 36), with retreatment allowed at ≥6-month intervals. Patients needing other macular oedema (ME) therapy exited the study. Changes from baseline in CSRT, macular volume and ME grade, area of retinal thickening, macular leakage, macular capillary loss and diabetic retinopathy severity were assessed. RESULTS After 3 years, more eyes treated with DEX implant 0.7 and 0.35 mg than sham showed improvement (although small) in ME grade (p<0.05 vs sham). DEX implant 0.7 mg delayed time to onset of two-step progression in diabetic retinopathy severity by ∼12 months. DEX implant 0.7 and 0.35 mg produced small, non-sustained reductions in macular leakage but had no significant effect on macular capillary loss. CONCLUSIONS DEX implant 0.7 or 0.35 mg, administered at ≥6-month intervals over 3 years, produced sustained retinal structural improvement in DME. TRIAL REGISTRATION NUMBER NCT00168337 and NCT00168389.
-
7.
Screening for diabetic retinopathy using new mydriasis-free, full-field flicker ERG recording device.
Fukuo, M, Kondo, M, Hirose, A, Fukushima, H, Ikesugi, K, Sugimoto, M, Kato, K, Uchigata, Y, Kitano, S
Scientific reports. 2016;:36591
Abstract
Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Therefore, it is important to detect DR accurately during mass screening. The purpose of this study was to determine whether a small, hand-held, mydriasis-free, full-field flicker electroretinographic (ERGs) device called RETeval can be used to screen for DR. To accomplish this, we recorded full-field flicker ERGs with this device from 48 normal eyes and 118 eyes with different severities of DR in patients with diabetes mellitus (DM). This system delivered a constant flash retinal luminance by adjusting the flash luminance that compensated for changes in the pupil size. Our results showed that there were significant correlations between the severity of DR and the implicit times (P < 0.001; r = 0.55) and the amplitudes (P = 0.001; r = -0.29). When the implicit time was used for the index, the area under the receiver operating characteristic curve was 0.84 for the detection of DR, and was 0.89 for the detection of DR requiring ophthalmic treatments. These results suggest that the implicit times of the flicker ERGs recorded by the small, mydryasis-free ERG system can be used as an adjunctive tool to screen for DR.
-
8.
Morphometric analysis of small arteries in the human retina using adaptive optics imaging: relationship with blood pressure and focal vascular changes.
Koch, E, Rosenbaum, D, Brolly, A, Sahel, JA, Chaumet-Riffaud, P, Girerd, X, Rossant, F, Paques, M
Journal of hypertension. 2014;(4):890-8
-
-
Free full text
-
Abstract
OBJECTIVES The wall-to-lumen ratio (WLR) of retinal arteries is a recognized surrogate of end-organ damage due to aging and/or arterial hypertension. However, parietal morphometry remains difficult to assess in vivo. Recently, it was shown that adaptive optics retinal imaging can resolve parietal structures of retinal arterioles in humans in vivo. Here, using adaptive optics retinal imaging, we investigated the variations of parietal thickness of small retinal arteries with blood pressure and focal vascular damage. METHODS Adaptive optics imaging of the superotemporal retinal artery was done in 49 treatment-naive individuals [mean age (±SD) 44.9 years (±14); mean systolic pressure 132 mmHg (±22)]. Semi-automated segmentation allowed extracting parietal thickness and lumen diameter. In a distinct cohort, adaptive optics images of arteriovenous nicking (AVN; n = 12) and focal arteriolar narrowing (FAN; n = 10) were also analyzed qualitatively and quantitatively. RESULTS In the cohort of treatment-naive individuals, by multiple regression taking into account age, body mass index, mean, systolic, diastolic and pulse blood pressure, the WLR was found positively correlated to mean blood pressure and age which in combination accounted for 43% of the variability of WLR. In the cohort of patients with focal vascular damage, neither FANs or AVNs showed evidence of parietal growth; instead, at sites of FANs, decreased outer diameter suggestive of vasoconstriction was consistently found, while at sites of AVNs venous narrowing could be seen in the absence of arteriovenous contact. CONCLUSION High resolution imaging of retinal vessels by adaptive optics allows quantitative microvascular phenotyping, which may contribute to a better understanding and management of hypertensive retinopathy.
-
9.
Comprehensive detection, grading, and growth behavior evaluation of subthreshold and low intensity photocoagulation lesions by optical coherence tomographic and infrared image analysis.
Koinzer, S, Caliebe, A, Portz, L, Saeger, M, Miura, Y, Schlott, K, Brinkmann, R, Roider, J
BioMed research international. 2014;:492679
Abstract
PURPOSE To correlate the long-term clinical effect of photocoagulation lesions after 6 months, as measured by their retinal damage size, to exposure parameters. We used optical coherence tomographic (OCT)-based lesion classes in order to detect and assess clinically invisible and mild lesions. METHODS In this prospective study, 488 photocoagulation lesions were imaged in 20 patients. We varied irradiation diameters (100/300 µm), exposure-times (20-200 ms), and power. Intensities were classified in OCT images after one hour, and we evaluated OCT and infrared (IR) images over six months after exposure. RESULTS For six consecutive OCT-based lesion classes, the following parameters increased with the class: ophthalmoscopic, OCT and IR visibility rate, fundus and OCT diameter, and IR area, but not irradiation power. OCT diameters correlated with exposure-time, irradiation diameter, and OCT class. OCT classes discriminated the largest bandwidth of OCT diameters. CONCLUSION OCT classes represent objective and valid endpoints of photocoagulation intensity even for "subthreshold" intensities. They are suitable to calculate the treated retinal area. As the area is critical for treatment efficacy, OCT classes are useful to define treatment intensity, calculate necessary lesion numbers, and universally categorize lesions in clinical studies.
-
10.
Diffusion tensor imaging of the optic nerve in multiple sclerosis: association with retinal damage and visual disability.
Smith, SA, Williams, ZR, Ratchford, JN, Newsome, SD, Farrell, SK, Farrell, JA, Gifford, A, Miller, NR, van Zijl, PC, Calabresi, PA, et al
AJNR. American journal of neuroradiology. 2011;(9):1662-8
Abstract
BACKGROUND AND PURPOSE There is a well-known relationship between MS and damage to the optic nerve, but advanced, quantitative MR imaging methods have not been applied to large cohorts. Our objective was to determine whether a short imaging protocol (< 10 minutes), implemented with standard hardware, could detect abnormal water diffusion in the optic nerves of patients with MS. MATERIALS AND METHODS We examined water diffusion in human optic nerves via DTI in the largest MS cohort reported to date (104 individuals, including 38 optic nerves previously affected by optic neuritis). We also assessed whether such abnormalities are associated with loss of visual acuity (both high and low contrast) and damage to the retinal nerve fiber layer (assessed via optical coherence tomography). RESULTS The most abnormal diffusion was found in the optic nerves of patients with SPMS, especially in optic nerves previously affected by optic neuritis (19% drop in FA). DTI abnormalities correlated with both retinal nerve fiber layer thinning (correlation coefficient, 0.41) and loss of visual acuity, particularly at high contrast and in nerves previously affected by optic neuritis (correlation coefficient, 0.54). However, diffusion abnormalities were overall less pronounced than retinal nerve fiber layer thinning. CONCLUSIONS DTI is sensitive to optic nerve damage in patients with MS, but a short imaging sequence added to standard clinical protocols may not be the most reliable indicator of optic nerve damage.