Christoph R. Clemens

Functional and anatomical results after a single intravitreal Ozurdex injection in retinal vein occlusion: a 6-month follow-up – The SOLO study

Purpose: To evaluate the efficacy of intravitreal dexamethasone implants in eyes with cystoid macular oedema (CME) secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) in the clinical everyday practice, examine the effects of early retreatment and compare the results with the GENEVA study.

Prediction of retinal pigment epithelial tear in serous vascularized pigment epithelium detachment.

Purpose:  The aim of the study was to identify predictive factors for detection of impending retinal pigment epithelium (RPE) tears in patients under anti‐VEGF therapy for treatment of retinal pigment epithelial detachment (PED) due to exudative age‐related macular degeneration (AMD) using near‐infrared reflectance imaging (NIR), spectral‐domain optical coherence tomography (SD‐OCT) and fluorescein angiography (FLA).

Multifocal Electroretinography in Eyes with Reticular Pseudodrusen

PURPOSE The aim of our study was to evaluate the impact of reticular pseudodrusen (RPD) on retinal function by multifocal electroretinography (mfERG), and combined simultaneous confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT). METHODS We included 19 eyes of 15 patients with RPD in the posterior pole and no other phenotypic retinal alteration were included (7 females and 8 males, age 77.2 ± 5.1 years) as well as 24 eyes of 17 healthy control subjects (7 females and 10 males, age 73.2 ± 5.9 years). All patients underwent fundus photography, SD-OCT, fluorescence angiography (FA), fundus autofluorescence, and near-infrared reflectance cSLO. mfERG measurements were performed by stimulating the retina by a field of 103 hexagons covering an area of approximately 30°. Amplitudes and latencies of focal retinal responses obtained at affected and nonaffected sites of RPD eyes and retinal responses of healthy control subjects were compared. RESULTS In all included study eyes, RPD stages 1-3 could be demonstrated clearly in SD-OCT, FA, and cSLO. The mean amplitudes measured in the areas affected by RPD were 12.5 to 53.1 nV/deg² (control group 19.4-50.1 nV/deg²). The mean latencies were 33.2 to 41.3 ms (control group 33.6-39.7 ms). mfERG amplitudes and latencies of retinal areas affected by RPD were not altered significantly when compared to corresponding nonaffected areas. CONCLUSIONS mfERG measurements did not show a definite influence on electrophysiologic activity in retinal areas affected exclusively with RPD.

Subretinal drusenoid deposits associated with pigment epithelium detachment in age-related macular degeneration.

Purpose: To characterize retrospectively subretinal drusenoid deposits (SDD) in patients with pigment epithelium detachment (PED) secondary to age-related macular degeneration. Methods: Confocal scanning laser ophthalmoscopy near-infrared reflectance images (820 nm) were recorded in 208 eyes of 104 patients with serous, drusenoid, or vascularized PED because of age-related macular degeneration in at least 1 eye. The digital images were evaluated by two independent readers with subsequent senior reader arbitration for prevalence of SDD. Results: Serous PED was present in only two patients and was therefore not included in the statistical analysis. Subretinal drusenoid deposits were detected in 55 of 102 (53.9%) patients in at least 1 eye. Forty-six of those 55 patients showed SDD bilaterally (83.6%). Subretinal drusenoid deposits were present in 51 (50%) right eyes and 50 (49.0%) left eyes. One hundred and forty-six of 204 eyes showed a PED secondary to age-related macular degeneration of which 111 (76%) were vascularized and 35 (24%) drusenoid. Prevalence of SDD was correlated with age (P < 0.0001) and female gender (P = 0.014), but not with the type of PED (P = 0.174). Cohen kappa statistics showed good interobserver agreement for infrared imaging (0.78 for right eyes, 0.74 for left eyes). Conclusion: Subretinal drusenoid deposits represent a common phenotypic characteristic in eyes with PED because of age-related macular degeneration . As described in previous studies, SDD are readily identified using confocal scanning laser ophthalmoscopy imaging technology. Future studies should pursue the pathophysiologic role and the predictive value of the presence of SDD in the development of PED and a subsequent rip of the retinal pigment epithelium.

Longitudinal structure function analysis in reticular pseudodrusen

PURPOSE To describe longitudinal structure/function correlations in eyes with progressive reticular pseudodrusen (RPD). METHODS Thirteen eyes of 12 patients with exclusively RPD in the posterior pole were included (75.1 ± 5.7 years). All patients underwent spectral-domain optical coherence tomography (SD-OCT), confocal scanning laser ophthalmoscopy (cSLO), and multifocal electroretinography (mfERG) at baseline and 12-month follow-up. Size of retinal area affected by RPD, number and stages of RPD lesions, and choroidal thickness (CT) were quantified at baseline and at follow-up visit. Amplitudes obtained by mfERG in RPD eyes at baseline and follow-up were analyzed and correlated to morphologic changes. Eyes were compared to those of age-matched healthy controls. RESULTS The total number of RPD lesions increased from 540 at baseline to 667 at 12-month follow-up. Mean CT was 198.5 ± 69.3 μm at baseline (control group 263.5 ± 42.6 μm; P = 0.005) and 189.2 ± 65.3 μm at follow-up (P < 0.001) (control group 265 ± 47.8 μm; P = 0.74). A mean growth of RPD-affected area of 3.3 mm(2) was measured. Multifocal ERG amplitudes decreased in both the study and control groups to a similar extent. Amplitudes differed significantly at the follow-up time point when compared between RPD-affected and nonaffected areas within the same eye. No correlations between changes of morphologic parameters and mfERG amplitude changes were found. CONCLUSIONS Multifocal ERG allows for detecting a decline of function over time in eyes with progressive RPD. Yet functional decline could not be correlated to changes in individual morphologic parameters.

Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring

Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularised RPE detachment due to age-related macular degeneration (AMD), and they usually involve a deleterious loss in visual acuity. Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies as well as a temporal association between the tear event and the intravitreal injection. As the number of AMD patients and the number of administered anti-VEGF injections increase, both the challenge of RPE tear prevention and the treatment after RPE tear formation have become more important. At the same time, the evolution of retinal imaging has significantly contributed to a better understanding of RPE tear development in recent years. This review summarises the current knowledge on RPE tear development, predictive factors, and treatment strategies before and after RPE tear formation.

High-resolution optical coherence tomography of subpigment epithelial structures in patients with pigment epithelium detachment secondary to age-related macular degeneration

Background The pathophysiology of pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD) is as yet incompletely understood and treatment remains challenging. Spectral domain optical coherence tomography (SD-OCT) allows for improved morphological characterisation of the space underneath the retinal pigment epithelium (RPE). Objective To investigate eyes with PED for structures underneath the detached RPE cell layer. Methods In a retrospective observational case study, SD-OCT scans of AMD-related PEDs were assessed for the presence of distinctive morphological features in the space between the detached RPE and inner Bruchs membrane. Results Structures present in the space between the detached RPE and Bruchs membrane were found in 14 of 90 eyes with AMD-related PED. Each of these eyes shows hyper-reflective material underneath the PED, presenting as highly reflective, multilayered, laminar structures, usually orientated parallel to Bruchs membrane. Conclusions The findings indicate that SD-OCT may be useful for a more refined phenotypic stratification of AMD-associated PED. Further studies are warranted to explore the correlates on other imaging modalities, to investigate the composition of this material and to assess the potential prognostic relevance of this new finding.

Quantification Of Retinal Pigment Epithelium Tear Area In Age-related Macular Degeneration

Purpose: To compare different quantification tools based on confocal scanning laser ophthalmoscopy for assessment of retinal pigment epithelium (RPE) tear area size. Methods: Confocal scanning laser ophthalmoscopy fundus autofluorescence (FAF) and near-infrared reflectance (IR) images were retrospectively evaluated in 23 patients with RPE tear after intravitreal injection for pigment epithelium detachment due to exudative age-related macular degeneration at baseline and additionally in 11 patients after 5.1 ± 1.8 months of follow-up. Retinal pigment epithelium tear area was measured by three independent readers using three methods: manually on confocal scanning laser ophthalmoscopy FAF images, manually on confocal scanning laser ophthalmoscopy IR images, and using an FAF-based semiautomated software. Results: Confidence intervals were 0.08 and 0.12 for FAF, 0.11 and 0.09 for FAF-based semiautomated software, and 0.25 and 0.27 for IR for intraobserver (Reader 1) and interobserver agreements (Readers 1 and 2), respectively. The average values of the square errors of the quantification methods were 0.040 ± 0.033 mm2 (FAF), 0.035 ± 0.060 mm2 (software), and 0.187 ± 0.219 mm2 (IR). Mean area of RPE tears at baseline given as the average measurement of all 3 readers using FAF-based semiautomated software was 5.77 ± 4.62 mm2 (range, 0.13–14.74 mm2). Follow-up measurements of unilobular RPE tears (8 patients) showed no change in lesion area size (0.14 ± 0.33 mm2); in contrast, multilobular RPE tears (3 patients) showed a progression in lesion area size of 1.80 ± 0.74 mm2. Conclusion: Manual FAF-based and semiautomated FAF-based quantifications of RPE tear area are accurate and reproducible and superior to manual IR-based measurement. Retinal pigment epithelium tear area quantification is clinically relevant regarding further intravitreal treatment, particularly in multilobular RPE tears.

Vitreous traction after Ozurdex injection.

Dear Editor: We read with great interest the article by Bakri and Omar describing the formation of a vitreomacular traction after an uneventful intravitreal Ozurdex injection. We can confirm this rare clinical event, as we observed the onset and formation of a macular hole 12 days after an uneventful Ozurdex injection (Fig. 1). We suggest that the cause of macular hole formation is rooted in the transient injection dynamics and that the macular hole appeared immediately after the implantation. Presumably, the patient did not realize it himself as visual acuity was only 0.05 before injection. The first optical coherence tomography-based control examination was performed 12 days after ozurdex implantation when the macular hole was detected for the first time. The formation of macular holes result from tangential traction at the posterior pole in eyes with firm vitreoretinal adhesions. A sudden traction on the vitreous, as frequently seen during sudden vacuum aspiration before laser-assisted in situ keratomileusis or YAG-capsulotomy, may increase tractional shear forces on the vitreomacular surface, inducing the formation of a macular hole. Bertelmann et al. have recently determined a high incidence of vitreoretinal adhesions in eyes with retinal vein occlusion compared to an age-matched group. About 72% of patients aged 65–69 presented an attached posterior vitreous in healthy eyes compared with 100% in central retinal vein occlusion, and 89% in branch retinal vein occlusion. The reported development of a vitreomacular traction after an Ozurdex injection in an eye with central retinal vein occlusion (CRVO) may indicate that the velocity during the application could cause drag force on the vitreous gel, inducing vitreoretinal traction at the posterior pole. In an experimental study with a high-speed camera, Meyer et al. measured the muzzle velocity during the application of Ozurdex implants and confirmed its high initial velocity. High-speed real-time recordings revealed that the entire movement of the dexamethason (DEX)-implant lasted between 28 and 55 ms in water (group A; n = 7) and 1–7 ms in vitreous (group B; n = 7) filled tanks. The implants moved with a mean muzzle velocity of 820 – 350 mm/s [ – standard deviation (SD), range 326–1349 mm/s] in group A and 817 – 307 mm/s ( – SD, range 373–1185 mm/s) in group B. In both groups, the implant gradually decelerated due to drag force. With greater distances, the velocity of the DEX-implant decreased exponentially to a complete stop at 13.9–24.7 mm in group A and at 6.4–8.0 mm in group B. Five DEX-implants in group A reached a total distance of more than 15 mm and their calculated mean velocity at a retinal impact of 15 mm was 408 – 145 mm/s ( – SD, range 322–667 mm/s) and the consecutive normalized energy was 0.55 – 0.44 J/m ( – SD). In group B, none of DEX-implants reached a total distance of 15 mm or more. The muzzle velocity of the DEX-implant of*0.8 m/s decreases exponentially over distance. The measured drag force decreases faster in vitreous than in water. The impact energy of the implant on the projected retinal area does not reach reported damage levels as for foreign bodies or other projectiles. The measurements indicate that the application is safe and that the directly applied energy of the implant does not induce any damage to the retinal surface. However, the initial high velocity of the implant entering the vitreous

Macular Hole Formation in the Presence of a Pigment Epithelial Detachment After Three Consecutive Intravitreal Antivascular Endothelial Growth Factor Injections

PURPOSE The aim of this study was to demonstrate the development of a macular hole (MH) and vitreomacular attachment (VMA) after treatment of a subfoveal pigment epithelial detachment (PED) by 3 consecutive antivascular endothelial growth factor (VEGF) injections in a patient with age-related macular degeneration (AMD). METHODS A 67-year-old woman with a subfoveal PED and occult choroidal neovascularization received 3 consecutive intravitreal ranibizumab injections in her left eye. Her initial visual acuity (VA) was 20/30. RESULTS Her VA stabilized at 20/30 at 3 months after the last injection; however, cross-sectional scans using optical coherence tomography (OCT) demonstrated a small vitreous attachment on the retinal surface at the foveola. Two months later, her VA was decreased to 20/100, and on biomicroscopy there was a positive Watzke sign on the center of the PED. OCT disclosed an increased VMA with a full-thickness MH. The perpendicular retina was elevated, whereas the PED appeared stabile. CONCLUSION Consecutive intravitreal injections may alter the vitreous gel, thus inducing a posterior vitreous detachment or VMA. New symptoms after the uploading phase with decreased VA or metamorphopsia may not necessarily relate to a progression of the AMD, but may also relate to a novel incomplete posterior vitreous vitreomacular traction possibly triggering the formation of traction and MH formation.