Milena Pahlitzsch

Conjunctival Melanoma and BRAF Inhibitor Therapy

Background: BRAF is a proto-oncogene that encodes the protein B-Raf. This is a serine/threonine kinase and part of the mitogen-activated protein kinase (MAPK) pathway. Vemurafenib is a potent inhibitor of the mutant BRAF. It is approved for cutaneous melanoma.Patient/methods: A 80-year-old woman presented with irregular pigmented, hyperaemic upper and lower eye lid changes and alterations in the temporal conjunctiva of the right eye 03/2011. A conjunctival melanoma was detected with expression of BRAF Mutation on exon 15 (by PCR). For causal therapy the only primary surgical option was offered: exenteration of the right orbital. The patient refused this surgical intervention. To stabilize and prevent progression of the lesions, treatment with a BRAF inhibitor (vemurafenib) has been started over 16 month period of time.Results: After successful tumour response and decreasing size complete resection was performed 08/2013. The therapy was terminated due to a controlled tumour situation and progressive deterioration of general condition 09/2013. The progression of conjunctival melanoma could be prevented by this therapy by now.Discussion: To the best of our knowledge it is the first case to show the permanent recovery of a conjunctival melanoma after BRAF inhibitor therapy. Over the course of time there was a significant reduction of the patient’s general condition including weight loss, vomiting, headaches. These side effects should be carefully evaluated in further studies.

Poppers Maculopathy: Complete Restitution of Macular Changes in OCT after Drug Abstinence

Abstract Background: “Poppers” is a slang term for a group of alkyl nitrites that are used as recreational drugs. Their inhalative intoxication leads to muscle relaxation, analgesia, and euphoria. Maculopathy is a rare but serious side-effect. Patients/Methods: Clinical, imaging, and electrophysiological findings of seven patients with maculopathy after consumption of poppers were presented. Results: All seven patients were male with a median age of 35 years (range 28–45 years), the median duration of periodical poppers use until the onset of symptoms was 9.8 years (one day to 25 years). Five of seven patients were HIV-positive, one patient was negative, and the HIV-status of one patient was unknown. Median average of visual acuity at presentation was 20/30 in each eye. In all patients, optical coherence tomography (OCT) showed pathognomonic alterations of the outer foveal retina. One patient showed an almost complete restitution of the maculopathy six months after cessation of drug use and following the oral intake of Lutein. Imaging alterations returned to normal and visual acuity recovered from 20/50 and 20/30 (right and left eye, respectively) to 20/20 on both eyes. Follow up of two other cases showed no relevant functional decline or improvement. Discussion: Toxic maculopathy due to the consumption of poppers is an important differential diagnosis in acute visual loss without clinico-morphological correlate. Optical coherence tomography is the only reliable diagnostic tool in these cases. Complete recovery of visual function and macular morphology is rare, even after cessation of drug abuse. Oral lutein therapy may have a beneficial effect.

Impact of the Femtosecond Laser in Line with the Femtosecond Laser-Assisted Cataract Surgery (FLACS) on the Anterior Chamber Characteristics in Comparison to the Manual Phacoemulsification

ABSTRACT Purpose: To assess the alterations of the anterior chamber conditions including laser flare photometry after femtosecond laser-assisted cataract surgery (FLACS) compared to the manual phacoemulsification. Methods: Data of n=70 FLACS (mean age 67.2 ± 8.9 years) and n=40 manual phacoemulsification (mean age 69.5 ± 9.6 years) were analyzed. The procedures were performed by LenSx Alcon, USA, and Alcon Infiniti Vision System, USA. The following parameters were recorded: laser flare photometry (Kowa FM 700, Japan), anterior chamber (AC) depth, AC volume, AC angle (Pentacam, Oculus Inc., Germany), lens density, pupil diameter, endothelial cell count and pachymetry. The analysis was performed preoperatively, immediately after femtosecond laser procedure and one day postoperatively. Results: Between FLACS and the phaco control group, there was a significant difference in the AC depth (p=0.023, 3.77 mm vs. 4.05 mm) one day postoperatively. The AC angle (p=0.016) showed a significant difference immediately after the femto laser treatment. The central and thinnest pachymetry and endothelial cell count did not show a significant difference between the two study cohorts (p=0.165, p=0.291, p=0.979). The phaco cohort (n=40) demonstrated a non-statistically significant difference in the flare photometry of 15.80 photons/ms one postoperative day compared to the FLACS group 26.62 photons/ms (p=0.322). Conclusion: In this study population, no evidence for an additive damage caused by the use of the femtosecond laser was demonstrated. Furthermore, no increase in the central and thinnest corneal thickness and no increased endothelial cell loss was demonstrated by the laser energy.

Accuracy of wavefront aberrometer refraction vs manifest refraction in cataract patients: impact of age, ametropia and visual function

BackgroundTo evaluate accuracy of WASCA wavefront aberrometry (WA) refraction in comparison to manifest refraction (MR) in an older population awaiting cataract surgery.MethodsProspectively, refractive errors of 130 eyes were determined by WA and MR. Mean age was 65.9 (SD 11.81), corrected distance visual acuity (CDVA) averaged 0.20 logMar (SD 0.57), mean manifest sphere was 0.23 dioptres (D, SD 3.39) and manifest astigmatism amounted to −1.25 D (SD 1.21). For further analysis, refractive values were transformed into power vector components: spherical equivalent (SE), Jackson cross cylinder at 0° and 45° (J0 and J45). The ‘limits of agreement’ approach, regression analysis, correlation analysis, and ANOVA were applied and additionally compared to 28 healthy eyes (mean VA −0.1 logMAR) of a group of young subjects (mean age 33.9).ResultsSE measures in myopia correlated highly between WA and MR (r = 0.917, p < .001). In hyperopia this correlation was moderately high (r = 0.800, p < .001). For all subjects, correlations between WA and MR for J0 and J45 were r = 0.742 (p < .001) and r = 0.760 (p < .001) respectively. WA measurements revealed larger agreement ranges with increasing myopia and astigmatism. Controlled for possible confounding variables of age, VA, and refractive state, no statistically significant effects were found. Across nearly all conditions, WA measured significantly higher myopic and astigmatic values than MR. Most effects were replicated in the reference group.ConclusionsWA refraction can provide valuable information in previously under-researched conditions such as reduced VA (cataract-related), advanced age, and hyperopia. However, loss of optical media transparency will inherently reduce accuracy of WA. Further studies are needed to define cut-off values for automated wavefront quality grading and intra-operative application of WA in refractive surgery.

Trabekulotomie ab interno (Trabectome) – Kumulierte klinische Ergebnisse eines großen Glaukomkollektivs

BACKGROUND To assess the outcome of routine trabectomy surgery in the treatment of primary (POAG) and secondary open angle glaucoma. PATIENTS/METHODS 296 eyes of 296 patients with diagnosed open angle glaucoma and exfoliative glaucoma were analysed from June 2012 until June 2014. IOP readings (intraocular pressure) and the number of antiglaucoma medications was evaluated at every follow-up visit. For statistical analysis, 4 study cohorts were built (cohort 1 = trabectomy in POAG, cohort 2 = trabectomy in exfoliative glaucoma (PEX), cohort 3 = trabectomy + IOL in POAG, cohort 4 = trabectomy + IOL in PEX glaucoma). RESULTS Mean IOP before trabectomy surgery was 19.8 ± 5.9 mmHg and 23.7 ± 9.5 mmHg in cohorts 1 and 2, respectively. At 1 year follow-up, IOP was reduced to normal level for cohorts 1 and 2 (14.8 ± 3.2 mmHg (p = 0.001) and 14.0 ± 3.3 mmHg (p = 0.046), respectively). The number of topical antiglaucoma medications changed to 2.1 ± 1.2 (p = 0.004) and 2.4 ± 1.2, respectively (p = 0.593) at one year follow-up, respectively, for POAG and exfoliative glaucoma. In study cohort 3 and 4, mean IOP before trabectomy surgery was 19.2 ± 4.0 mmHg and 23.2 ± 9.2 mmHg, respectively. At 1 year follow-up, IOP was reduced to normal levels in cohorts 3 and 4 (11.8 ± 3.1 mmHg (p < 0.01) and 12.6 ± 1.1 mmHg, respectively (p = 0.043)); the number of topical antiglaucoma medications changed to 2.3 ± 1.4 (p = 0.469) and 1.4 ± 0.8, respectively, (p = 0.102) at 1 year follow-up. A significant difference in IOP reduction could be demonstrated in POAG between the trabectomy + IOL group and the trabectomy cohort 1 year postoperative (p = 0.017); in the PEX trabectomy + IOL versus PEX trabectomy cohort no statistically significant difference (p = 0.678) could be demonstrated. No serious postoperative complications were recorded. CONCLUSION Trabectomy surgery seemed to be a reliable and effective tool for the management of mild and moderate primary and secondary open angle glaucoma with uncontrolled IOP in daily routine. One year follow-up showed a significant reduction in intraocular pressure in all cohorts.

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.

Significance of the disc damage likelihood scale objectively measured by a non-mydriatic fundus camera in preperimetric glaucoma

Purpose To assess the correlation between the disc damage likelihood scale (DDLS) objectively measured by a non-mydriatic fundus camera, Heidelberg Retina Tomograph 3, and optic coherence tomography in preperimetric glaucoma. Methods One-hundred-twenty-five patients with preperimetric primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (n=30) were included (mean age 58.9±15.9 years). All three devices graded the optic disc topography: Diagnosis 1 was defined as “outside normal limits”, while Diagnosis 2 as “borderline or outside normal limits”. Results For Diagnosis 1, a significant correlation was shown between DDLS and Moorfields regression analysis (P=0.022), and for Diagnosis 2 with glaucoma probability score analysis (P=0.024), in POAG. In pseudoexfoliation glaucoma, DDLS did not correlate significantly with Heidelberg Retina Tomograph 3 and optic coherence tomography. Regarding the area under the curve the highest predictive power was demonstrated by the objective DDLS (0.513–0.824) compared to Burk (0.239–0.343) and Mikelberg (0.093–0.270) coefficients. Conclusions The DDLS showed a significant correlation to the Moorfields regression analysis in preperimetric POAG. The objective DDLS showed the highest predictive power and thus is an additive tool in diagnosing preperimetric glaucoma.

Comparison of dynamic contour tonometry versus Goldmann applanation tonometry according to the International Ocular Tonometer Standards ISO 8612 in glaucoma patients

INTRODUCTION The aim of this study was to compare the dynamic contour tonometry PASCAL® (DCT) versus the Goldmann applanation tonometry (GAT) in a glaucoma population and to analyse the correlation with the central corneal thickness (CCT). PATIENTS/METHODS 191 eyes of 107 Caucasian glaucoma patients (62 female, 45 male) were included: 3 repeated GAT and dynamic contour tonometry (DCT) measurements (quality factor 1-2) were analysed. CCT was measured by ultrasound pachymetry. Criteria of ISO 8612 were fulfilled: 3 groups of IOP measurements were formed: group 1: 7-16 mmHg, group 2: 16-23 mmHg and group 3: > 23 mmHg, each including at least 40 eyes. Only 5.0 % outliers per area of intraocular pressure were permitted in a tolerance of ± 5.0 mmHg. RESULTS Data of 191 eyes (mean CCT 553 µm) were analysed. GAT (19.68 mmHg ± 7.56 mmHg) showed good correlation to DCT (20.54 ± 8.21 mmHg) (r = 0.770, p < 0.001). Mean difference DCT-GAT was 0.86 ± 2.45 mmHg. In regard to the criteria of ISO 8612, the number of outliers were: group 1: (n = 68) 29.4 %, group 2: (n = 62) 41.9 %, and group 3: (n = 61) 31.2 %. No correlation was shown between CCT vs. GAT (r = 0.184, p = 0.057) and CCT vs. DCT (r = 0.177, p = 0.09), respectively. DISCUSSION In conclusion, despite good correlation to GAT measurements DCT does not fulfil the ISO 8612 reference criteria in glaucoma patients. DCT and GAT did not show correlation to CCT.

Secondary glaucoma in uveitis: comparison of the optic nerve head morphology among a nonmydriatic fundus camera, HRT, and SD-OCT

Purpose: To assess the correlation between the disc damage likelihood scale (DDLS) objectively measured by a nonmydriatic fundus camera, confocal laser scanning ophthalmoscopy (HRT3), and spectral-domain optical coherence tomography (SD-OCT) in uveitic glaucoma. Methods: A total of 59 patients with uveitic glaucoma (21 female, 38 male; mean age 56.8 ± 18.7 years) were included in this prospective cross-sectional study. All patients were measured by the Kowa Nonmyd WX 3D camera (2D/3D nonmydriatic retinal camera, Kowa Company), the HRT3 (Heidelberg Engineering), and SD-OCT (Carl Zeiss Meditec) by one examiner on the same day. All 3 devices graded the optic disc topography. Statistical data were calculated using SPSS (v 20.0, SPSS). Results: In patients showing borderline results in one of the modalities (n = 45), the DDLS showed a significant correlation with the retinal nerve fiber layer (p = 0.016), while Moorfields regression analysis (p = 0.550) and glaucoma probability score (p = 0.629) did not correlate significantly. The highest predictive power was demonstrated by the objectively measured DDLS (area under the receiver operating characteristic curve 0.445-0.588), compared to R. Burk (0.149-0.375) and F.S. Mikelberg (0.033-0.450) coefficients considering HRT and optical coherence tomography. Conclusions: In this study cohort, the objective DDLS showed the highest predictive power and thus is a reliable tool in diagnosing uveitic glaucoma. These 3 devices cannot be used interchangeably. As diagnosis and follow-ups are challenging in uveitis patients, the stereophotography is additionally a valuable tool.

iStent inject as a reasonable alternative procedure following failed trabeculectomy

Purpose: The aim of this study is to assess the intraocular pressure lowering effect and the performance of the glaucoma therapy of the iStent inject in glaucoma patients with uncontrolled intraocular pressure after failed trabeculectomy. Methods: In this retrospective study, iStent inject implantation (Glaukos Corporation, Laguna Hills, CA, USA) was performed in 22 eyes of 21 subjects suffering from glaucoma (n = 18 primary open angle glaucoma, n = 3 pseudoexfoliation glaucoma, and n = 1 for secondary glaucoma) with an intraocular pressure above target pressure after failed trabeculectomy (mean = 9.6 ± 8.1 years; range: 1–35 years). The intraocular pressure and the number of antiglaucomatous medication were assessed preoperatively, 1 day, 6 weeks, 3 months, 6 months, and 1 year after surgery and compared to preoperative findings (SPSS v23.0; Shapiro–Wilk test, Wilcoxon test, Friedman test). Results: The results showed a significant intraocular pressure decrease from 22.5 ± 4.6 to 15.5 ± 3.4 mmHg after 1 year follow-up (p = 0.012). The glaucoma therapy was 2.6 ± 1.2 preoperatively and reduced to 2.25 ± 1.5 number of medications after 1 year (p > 0.05). There was no significant difference in the number of medication during the whole follow-up period (1 year, p = 0.012). No significant intra- or postoperative complications were reported. Conclusion: Minimal invasive glaucoma surgery (iStent inject) can offer an effective intraocular pressure reduction in advanced adult primary and secondary open angle glaucoma after failed trabeculectomy in a follow-up period of 1 year. Glaucoma therapy, however, needs to be maintained to achieve an individual target pressure and to prevent glaucoma progression. In addition, a failure rate of 27.3% makes it necessary to select carefully patients for this treatment option.