Daniel J. Salchow

Treatment of type I ROP with intravitreal bevacizumab or laser photocoagulation according to retinal zone

Aims To investigate the outcome of intravitreal bevacizumab (IVB) compared with laser photocoagulation in type I retinopathy of prematurity (ROP). Methods Case records of 54 consecutive very low birth weight (VLBW) infants with type I ROP (posterior ROP, n=33; peripheral zone II, n=21) who were treated either with IVB (n=37) or laser photocoagulation (n=17) between 2011 and 2015 were retrospectively evaluated. Results Patients with posterior ROP displayed significantly faster regression of active ROP within 12 days (range 9–15 days) if treated with IVB compared with laser photocoagulation, where active ROP regressed within 57 days (range 28–63 days) (p>0.001). No difference was observed in peripheral zone II. Five of seven patients (12%) who developed a recurrence in both eyes after IVB required additional laser photocoagulation within a mean of 12.7 weeks (11.3–15.6 weeks) after the previous treatment. After laser photocoagulation one patient with posterior ROP developed macular dragging and another patient developed a temporary exudative retinal detachment in both eyes. 12 months after treatment the spherical equivalent was not statistically significant different between IVB and laser photocoagulation in posterior ROP patients. However, IVB lead to a significant lower spherical equivalent in infants with posterior ROP (+0.37 dioptres, range −0.5 to +1.88 dioptres) compared with peripheral zone II (+3.0 dioptres range +2.0 to +4.0 dioptres, p<0.001). Conclusions IVB leads to faster regression of active ROP in infants with posterior ROP compared with laser photocoagulation. Spherical equivalent after 12 months was comparable in those treated with IVB and laser photocoagulation, but it was significantly lower in posterior ROP than in peripheral zone II.

Biometric and structural ocular manifestations of Marfan syndrome.

Background To study biometric and structural ocular manifestations of Marfan syndrome (MFS). Methods Observational, retrospective, comparative cohort study in a tertiary referral center on 285 MFS patients and 267 controls. Structural and biometric ocular characteristic were compared. Results MFS eyes were longer (axial length 24.25 ± 1.74 mm versus 23.89 ± 1.31 mm, p < 0.001) and had a flatter cornea than control eyes (mean keratometry 41.78 ± 1.80 diopters (D) versus 43.05 ± 1.51 D, p < 0.001). Corneal astigmatism was greater and the central cornea was thinner in MFS eyes (530.14 ± 41.31 μm versus 547.02 ± 39.18 μm, p < 0.001). MFS eyes were more myopic than control eyes (spherical equivalent -2.16 ± 3.75 D versus -1.17 ± 2.58 D, p < 0.001). Visual acuity was reduced (0.13 ± 0.25 logMAR versus 0.05 ± 0.18 logMAR, p < 0.001) and intraocular pressure was lower in MFS eyes (14.6 ± 3.4 mmHg versus 15.1 ± 3.2 mmHg, p = 0.01). Iris transillumination defects (ITD) were significantly more common in MFS eyes (odds ratio for MFS in the presence of ITD, 3.7). Ectopia lentis (EL) was only present in MFS eyes (33.4%). History of retinal detachment was significantly more common in MFS eyes. Glaucoma was equally common in both groups. Conclusions ITD and EL are most characteristic findings in MFS. ITD and corneal curvature should be studied as diagnostic criteria for MFS. Visual acuity is reduced in MFS. MFS patients need regular eye exams to identify serious ocular complications.

Influence of chloroquine intake on the multifocal electroretinogram in patients with and without maculopathy

PurposeTo evaluate the effect of long-term chloroquine intake on the multifocal electroretinogram (mfERG) in female patients with and without maculopathy.MethodsRetrospective analysis of the mfERGs recorded in three different groups: (1) patients with bilateral maculopathy having taken chloroquine, (2) patients without maculopathy having taken chloroquine, and (3) healthy control subjects (age-matched to group 2) who never took chloroquine. MfERGs of each group were averaged, and the data of each patient group were compared to the control group. The main outcome measures were N1 and P1 characteristics and the ring ratio analysis.ResultsIn group 1, 11 female subjects (22 eyes) were included, group 2 consisted of nine patients (18 eyes) and group 3 of seven healthy female subjects (14 eyes). Compared with healthy controls, patients in group 1 showed significantly reduced response densities of both N1 and P1 across all ring eccentricities except ring 5. Implicit times were significantly delayed only concerning N1 (ring 4 and the sum response of the left eye of group 1). P1 implicit times showed no significant alterations in either group. Ring ratios of the response densities were significantly higher mainly concerning group 1 (N1: ring 5/ring 2 and ring 5/ring 4 of the right eye; P1: all ring ratios of the right eye and all ratios except ring 5/ring 1 and ring 5/ring 4 of the left eye). The only ring ratio being significantly higher in group 2 was P1 ring 5/ring 1 ratio of the right eye.ConclusionsIn the absence of clinically apparent maculopathy, chloroquine intake was not associated with major alterations of the mfERG.

Branch Retinal Artery Occlusion without Morphologic orElectrophysiological Evidence

A 71-year-old man reported sudden, painless loss of the superior visual field of the right eye three days ago. Best-corrected visual acuity was 20/32 on the right and 20/25 on the left eye, a relative afferent pupillary defect was absent. Slitlamp-biomicroscy and dilated fundus exam were normal. Time-domain Optical Coherence Tomography (OCT) of the macula, pattern visual evoked potentials and multifocal electroretinography were normal. Magnetic resonance imaging of the brain showed an infarction located in the right parieto-occipital area, inconsistent with the visual field defect. 2 weeks later fundus examination showed two cholesterol emboli in the inferior temporal retinal artery, OCT showed retinal thinning of the inferior macula. Conclusion: Branch retinal artery occlusion may initially present without morphologic and electrophysiological evidence. Re-evaluation at a later time should reveal typical findings such as retinal thinning.

Ocular manifestations of Marfan syndrome in children and adolescents

Purpose: To study ocular manifestations of Marfan syndrome in children and adolescents. Methods: Retrospective comparative cohort study on consecutive patients up to age 17 years, presenting to the interdisciplinary Marfan clinic of Charité-University Medicine Berlin over a period of 4 years. Results: A total of 52 Marfan syndrome patients and 73 controls were enrolled. In Marfan syndrome eyes, the cornea was flatter (mean keratometry, 40.86 ± 2.13 vs 42.55 ± 1.55 diopters in control eyes, p < .001) and corneal astigmatism was greater (1.50 ± 1.22 vs 0.88 ± 0.49 diopters in control eyes, p < .001). The central cornea was thinner in Marfan syndrome eyes (537.35 ± 40.64 vs 552.95 ± 38.57 μm, p = 0.007) and Marfan syndrome eyes were more myopic than control eyes (spherical equivalent, –2.77 ± 4.77 vs −0.64 ± 1.92 diopters, p < .001). Visual acuity was reduced (logMAR 0.11 ± 0.17 vs 0.04 ± 0.26, p = 0.014) and intraocular pressure was lower in Marfan syndrome eyes. Iris transillumination defects were more common in Marfan syndrome eyes (19.6% vs 4.3% in control eyes, odds ratio for Marfan syndrome in the presence of iris transillumination defects = 7.2). Ectopia lentis was only found in Marfan syndrome eyes (25 Marfan syndrome patients, 49% with available data, bilateral in 68%). Conclusion: Iris transillumination defects and ectopia lentis are characteristic ocular findings in children and adolescents with Marfan syndrome. Myopia is more common and corneal curvature, central corneal thickness, and visual acuity are reduced in Marfan syndrome eyes. Children with Marfan syndrome need regular comprehensive eye examinations to identify potential complications.

Facilitating the analysis of the multifocal electroretinogram using the free software environment R

Purpose: The large amount of data rendered by the multifocal electroretinogram (mfERG) can be analyzed and visualized in various ways. The evaluation and comparison of more than one examination is time-consuming and prone to create errors. Using the free software environment R we developed a solution to average the data of multiple examinations and to allow a comparison of different patient groups. Methods: Data of single mfERG recordings as exported in .csv format from a RETIport 21 system (version 7/03, Roland Consult) or manually compiled .csv files are the basis for the calculations. The R software extracts response densities and implicit times of N1 and P1 for the sum response, each ring eccentricity, and each single hexagon. Averages can be calculated for as many subjects as needed. The mentioned parameters can then be compared to another group of patients or healthy subjects. Application of the software is illustrated by comparing 11 patients with chloroquine maculopathy to a control group of 7 healthy subjects. Results: The software scripts display response density and implicit time 3D plots of each examination as well as of the group averages. Differences of the group averages are presented as 3D and grayscale 2D plots. Both groups are compared using the t-test with Bonferroni correction. The group comparison is furthermore illustrated by the average waveforms and by boxplots of each eccentricity. Conclusions: This software solution on the basis of the programming language R facilitates the clinical and scientific use of the mfERG and aids in interpretation and analysis.

Activation of a Ca2+-dependent cation conductance with properties of TRPM2 by reactive oxygen species in lens epithelial cells

ABSTRACT Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca2+‐dependent non‐selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca2+‐ and reactive oxygen species (ROS)‐dependent non‐selective cation channels in human lens epithelial cells. RT‐PCR revealed gene expression of the Ca2+‐activated non‐selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE‐B3, whereas TRPM5 mRNA was only found in HLE‐B3 cells. Using whole‐cell patch‐clamp technique, ionomycin evoked non‐selective cation currents with linear current‐voltage relationship in both cell types. The current was decreased by flufenamic acid (FFA), 2‐APB, 9‐phenanthrol and miconazole, but insensitive to DIDS, ruthenium red, and intracellularly applied spermine. H2O2 evoked a comparable current, abolished by FFA. TRPM2 protein expression in HLE‐B3 cells was confirmed by means of immunocytochemistry and western blot. In summary, we conclude that lens epithelial cells functionally express Ca2+‐ and H2O2‐activated non‐selective cation channels with properties of TRPM2. HIGHLIGHTSmRNA expression of Ca2+ activated non‐selective cation channels in lens epithelial cells.Induction of non‐selective cation conductance in lens epithelial cells by [Ca2+]i.c. and [H2O2]e.c..Functional expression of a Ca2+‐activated non‐selective cation channel with properties of TRPM2.Protein expression of TRPM2 in HLE‐B3 cells.

Ocular findings in Loeys-Dietz syndrome

Background Loeys-Dietz syndrome (LDS), an autosomal-dominant connective tissue disorder, is characterised by systemic manifestations including arterial aneurysm and craniofacial dysmorphologies. Although ocular involvement in LDS has been reported, detailed information on those manifestations is lacking. Methods Retrospective chart review of patients with diagnosed LDS and comparison with age-matched control patients. Results Mean age was 37.8±14.6 years (patients with LDS) and 38.4±13.5 years (controls). Patients with LDS less frequently had iris transillumination, cataract and glaucoma compared with controls. Scleral and retinal vascular abnormalities were not found in any of the LDS eyes. Ectopia lentis was found in one patient with LDS. The eyes of patients with LDS tended to be more myopic (spherical equivalent, −2.47±2.70 dioptres (dpt) vs −1.30±2.96dpt (controls); P=0.08) and longer (24.6±1.7mm vs 24.1±1.5mm (controls); P=0.10). Central corneal thickness was significantly reduced in LDS eyes (521±48µm vs 542±37µm (controls); P=0.02). Corneal curvature (43.06±1.90dpt (LDS) versus 43.00±1.37dpt (controls); P=0.72) and interpupillary distance (65.0±6.0mm (LDS) vs 64.3±4.8mm (controls); P=0.66) did not differ significantly between both groups. Visual acuity was similar between both groups (0.03±0.09logarithm of the minimum angle of resolution (logMAR) for LDS eyes and 0.05±0.17logMAR for control eyes, P=0.47). Conclusions Ocular features of LDS include decreased central corneal thickness and mild myopia. Ectopia lentis may be slightly more common than in controls but appears less common than in Marfan syndrome. Hypertelorism, scleral and retinal vascular abnormalities were not features of LDS.

FUNDUS AUTOFLUORESCENCE FINDINGS IN EARLY CHLOROQUINE MACULOPATHY

Background/Purpose: Toxic maculopathy is a rare but severe complication of chloroquine intake. Although the phenotype of established maculopathy was analyzed in detail, few data exist on the ophthalmologic findings in the early stage. Methods: The authors present 4 female patients with unequivocal signs of chloroquine maculopathy (bilateral [peri-]central scotoma in the visual fields, structural alterations of the macula in the optical coherence tomography) but normal or atypical findings as to fundus autofluorescence imaging. Results: In all patients, optical coherence tomography showed perifoveal thinning and subtle alterations of the outer retinal layers. In one patient, the latter was limited to the pericentral region, whereas it showed a more diffuse distribution in two other patients. One patient showed a combination of pericentral and diffuse damage. Multifocal electroretinography was recorded in three patients and revealed the typical (peri-)central amplitude reductions. Conclusion: A normal fundus autofluorescence does not rule out toxic maculopathy. Optical coherence tomography and multifocal electroretinography seem to be more sensitive in the early stage of the disease. In case of typical complaints and visual fields, the optical coherence tomography has to be evaluated for subtle alterations of the outer retina. Their presence justifies the cessation of the drug. Multifocal electroretinography may be of special value in these problematic cases.

Inferior oblique recession in thyroid-related orbitopathy

Thyroid-related orbitopathy is a form of orbital inflammation associated with thyroid dysfunction, developing in many patients with Graves disease. Fibrosis of the inferior rectus muscle can lead to restricted elevation and vertical ocular misalignment, which may be improved by recessing this muscle. In some patients, vertical misalignment persists after surgical weakening of one or more vertical rectus muscles. In this case series, unilateral inferior oblique recession as a secondary procedure after inferior rectus recession reduced hypertropia in primary gaze from 9(Δ) ± 3(Δ) to 1.3(Δ) ± 1.5(Δ) (mean ± standard deviation) and largest hypertropia in side gaze from 18.3 ± 2.1(Δ) to 3.3(Δ) ± 1.5(Δ). Postoperatively, all 3 patients were diplopia free in primary and downgaze.