Maria Waizel

High frequency of MYD88 mutations in vitreoretinal B-cell lymphoma: a valuable tool to improve diagnostic yield of vitreous aspirates

Vitreoretinal diffuse large B-cell lymphoma is a rare disorder, occurring as primary ocular disease or as secondary involvement by primary central nervous system lymphoma. It is usually diagnosed by cytologic, immunocytochemical, and molecular examination of vitreous aspirates. However, distinguishing vitreoretinal diffuse large B-cell lymphoma from uveitis remains difficult, and clonality analysis may be either unsuccessful or misleading. Diffuse large B-cell lymphoma arising in immune-privileged sites (eg, the central nervous system) shows a high frequency of MYD88 mutations. Therefore, we retrospectively assessed the frequency of MYD88 mutations in vitreoretinal lymphoma (VRL) and their diagnostic potential in 75 vitrectomy samples of 69 patients, and validated our results in a separate cohort (n = 21). MYD88 mutations were identified in 20 of 29 (69%) clinically, histologically, and molecularly confirmed VRL, including 6 cases of the test cohort initially diagnosed as reactive (3/6) or suspicious (3/6) for lymphoma. MYD88 mutations, especially L265P, are very frequent in VRL and their detection significantly improves the diagnostic yield of vitrectomy specimens.

Efficacy of Vitrectomy Combined with Subretinal Recombinant Tissue Plasminogen Activator for Subretinal versus Subpigment Epithelial versus Combined Hemorrhages.

Background: The aim of this study was to compare the outcomes after subretinal recombinant tissue plasminogen activator (rtPA) treatment for subretinal hemorrhages (SRH), subpigment epithelial hemorrhages (SPH), and combined subretinal and subpigment epithelial hemorrhages (CH). Methods: An observational analysis of patients treated with subretinal rtPA was performed. The primary endpoint was the assessment of visual improvement (best-corrected visual acuity, BCVA) after surgery. Secondary endpoints were evaluation of the maximal hemorrhage diameter (MHD) and central macular thickness (CMT) measured by spectral domain optical coherence tomography. Results: From a total of 83 eyes included in the study, 19 eyes showed SRH, 11 eyes SPH, and 53 eyes CH. For SRH and CH, the mean BCVA, MHD, and CMT improved significantly (p < 0.05). For patients with SPH, both the mean MHD and CMT decreased significantly (p < 0.05), whereas the mean BCVA improved only slightly after surgery (p = 0.28). Conclusion: Vitrectomy combined with subretinal rtPA injection and gas or air tamponade has a strong functional and anatomical effect on both SRH and CH and also seems to slightly improve the anatomical outcome in SPH.

Response to bevacizumab after treatment with aflibercept in eyes with neovascular AMD

Purpose To study the visual outcome and change in central macular thickness (CMT) in patients with neovascular age-related macular degeneration (AMD) who were previously treated with aflibercept (VEGF Trap-Eye, Eylea) and were subsequently switched to bevacizumab (Avastin). Methods In this observational analysis, 19 eyes initially treated with at least 3 injections of bevacizumab after initial treatment with at least 3 injections of aflibercept are reported. Outcome measures were Snellen visual acuity (best-corrected visual acuity (BCVA) and CMT measured by spectral-domain optical coherence tomography. Results A total of 19 eyes initially treated with 6.5 ± 2.8 intravitreal injections of aflibercept were switched to 5.4 ± 3.2 injections of bevacizumab. Median BCVA decreased from 20/94 to 20/113 after aflibercept and increased slightly to 20/101 after bevacizumab (p = 0.84, Friedman test). Of all 19 eyes, 36.8% achieved gain in visual acuity of more than 1 line and 21.1% of more than 3 lines. The CMT decreased slightly from 433 ± 229 μm at baseline to 367 ± 198 μm after aflibercept treatment (p = 0.18, Wilcoxon test) and decreased statistically significantly to 335 ± 184 μm after bevacizumab treatment (p = 0.0065, Wilcoxon test). Conclusions Switching from aflibercept to bevacizumab treatment has an equivalent anatomical effect in eyes with neovascular AMD as switching from bevacizumab to aflibercept. Therefore, switching back to bevacizumab might represent a reasonable therapy strategy to overcome tachyphylaxis during long-term monotherapy with aflibercept.

Digital Pupillometry in Normal Subjects

ABSTRACT The aim of this study was to evaluate the pupil size of normal subjects at different illumination levels with a novel pupillometer. The pupil size of healthy study participants was measured with an infrared-video PupilX pupillometer (MEye Tech GmbH, Alsdorf, Germany) at five different illumination levels (0, 0.5, 4, 32, and 250 lux). Measurements were performed by the same investigator. Ninety images were executed during a measurement period of 3 seconds. The absolute linear camera resolution was approximately 20 pixels per mm. This cross-sectional study analysed 490 eyes of 245 subjects (mean age: 51.9 ± 18.3 years, range: 6–87 years). On average, pupil diameter decreased with increasing light intensities for both eyes, with a mean pupil diameter of 5.39 ± 1.04 mm at 0 lux, 5.20 ± 1.00 mm at 0.5 lux, 4.70 ± 0.97 mm at 4 lux, 3.74 ± 0.78 mm at 32 lux, and 2.84 ± 0.50 mm at 250 lux illumination. Furthermore, it was found that anisocoria increased by 0.03 mm per life decade for all illumination levels (R2 = 0.43). Anisocoria was higher under scotopic and mesopic conditions. This study provides additional information to the current knowledge concerning age- and light-related pupil size and anisocoria as a baseline for future patient studies.

The effect of autoimmune retinopathy on retinal vessel oxygen saturation

PurposeTo study the retinal vessel oxygen saturation alterations in patients with autoimmune retinopathy (AIR) and patients with autoimmune retinopathy associated with retinitis pigmentosa (AIR-RP) in comparison with healthy controls and patients with isolated retinitis pigmentosa (RP).DesignProspective, cross-sectional, and non-interventional study.SubjectsRetinal vessel oximetry (RO) was performed on a total of 139 eyes: six eyes suffering from AIR and four eyes with AIR-RP were compared to 59 healthy control eyes and to 70 eyes with RP.MethodsA computer-based program of the retinal vessel analyser unit (IMEDOS Systems UG, Jena, Germany) was used to evaluate retinal vessel oxygen saturation. The mean oxygen saturation in the first and second branch retinal arterioles (A-SO2) and venules (V-SO2) were measured and their difference (A-V SO2) was calculated. In addition, we measured the diameter of the retinal arterioles (D-A) and venules (D-V).Main outcome measuresOxygen metabolism is altered in patients with isolated AIR and AIR-RP.ResultsBoth, AIR and AIR-RP groups, differed from healthy controls showing significantly higher V-SO2 values and significantly lower A-V SO2 values (p < 0.025). In addition, the AIR-RP group could be differentiated from eyes suffering from isolated RP by means of significantly higher V-SO2 values. Comparing retinal vessel diameters, both, the AIR and AIR-RP groups, presented with significant arterial (p = 0.05) and venular (p < 0.03) vessel attenuation than the healthy control group.ConclusionsBased on our results, in analogy to patients suffering from RP, oxygen metabolism seems to be altered in AIR patients.

Structural and Functional Outcome of Vitrectomy Combined with Subretinal Recombinant Tissue Plasminogen Activator for Isolated Subpigment Epithelial Hemorrhages

cant, the best-corrected visual acuity of the SPH subgroup improved with an average gain of 1.1 lines. We therefore congratulate the authors for their very outstanding functional outcome from logMAR 1.20 to logMAR 0.60 one week after re-vitrectomy combined with subretinal rtPA and 25% SF6 gas tamponade. Anatomically, this could be explained, in fact, by drainage into the subretinal space, either through microruptures or through possible subclinical retinal pigment epithelial tear (RIP) formation. The optical coherence tomography scans provided in this case report could be interpreted as a limited RIP. We therefore recommend reviewing all available optical coherence tomography scans again. Nevertheless, even if a possible RIP might not be present in this case, a subretinal treatment for SPH needs to be discussed critically beforehand. For any manipulation below the retinal pigment epithelium, there must be considerations about a potential benefit against the risk of provoking a RIP. Our study results allow for a clinical presurgery assessment of the underlying case, based on its anatomical characteristics [2] . However, the case of Fotis et al. [1] is important, since it strikingly demonstrates the possibility of a SPH displacement with subretinal rtPA treatment. Dear Editor We are very grateful to Fotis et al. [1] for their interest in our recently published study [2] that presents the structural and functional outcome after pars plana vitrectomy combined with subretinal recombinant tissue plasminogen activator (rtPA) treatment for isolated subretinal, subpigment epithelial (SPH), and combined hemorrhages. Here, we would like to respond to the questions that were raised by the authors: We thank the authors for the presentation of their case report, which confirms the findings of our study that a patient with SPH may benefit from subretinal rtPA treatment, even if with a mainly anatomical improvement. However, the published case presents an exceptional and very convincing response to prompt and consequent subretinal rtPA treatment in an eye with a short hemorrhage duration of only 4 days. Unfortunately, since subretinal hemorrhages mostly occur in elderly patients, it is not uncommon that diagnosis and treatment starts with a delay of several days or even weeks. In our study, the mean duration of submacular hemorrhage was 11.1 ± 12.4 (mean ± SD) days before initiating surgery. Still, in those 11 eyes classified as isolated SPH, we found a strong anatomical but only a slight functional benefit following subretinal rtPA treatment. Although not statistically signifiReceived: April 8, 2017 Accepted: April 19, 2017 Published online: May 24, 2017

Author’s reply to comments to: Response to bevacizumab after treatment with aflibercept in eyes with neovascular AMD

larger number of patients included is needed to prove our preliminary results. 5. Our functional results were in accordance with other studies investigating the outcome after switching from ranibizumab and/or bevacizumab to aflibercept. Fassnacht-Riederle et al (3) found only slight functional improvements when switching to aflibercept after initial treatment with ranibizumab and/or bevacizumab: visual acuity increased about 1.8 letters in Early Treatment Diabetic Retinopathy Study visual acuity score but did not reach statistical significance. Bakall et al (4) found no significant change in visual acuity after a switch to aflibercept after initial treatment with ranibizumab and/or bevacizumab. Therefore, we postulate that in long-term use of anti-VEGF, basically one should not raise falsely high expectations for a significant functional improvement after switching between drugs.