The use of intraluminal PRESERFLO stenting in avoiding early postoperative hypotony.

PURPOSE: Postoperative hypotony following PRESERFLO MicroShunt (PMS) implantation is a frequent cause of complications such as choroidal detachment and hypotony maculopathy. This study aims at evaluating the impact of intraluminal stenting of the PMS during the early postoperative period. METHODS: We retrospectively analyzed the data of 97 patients who underwent PMS implantation with intraoperative placement of a Nylon 10-0 suture as intraluminal stent (PStent) and compared the outcomes to those of an existing database of the traditional MicroShunt implantation technique (PTrad, n = 120). The primary outcome measure was the intraocular pressure (IOP) at one week postoperatively. As a secondary outcome measure, adverse hypotony, defined as an IOP ≤ 5 mmHg with significant choroidal effusion and/or anterior chamber shallowing or the presence of macular folds was also assessed. Additionally, the time to stent removal and the IOP one week after stent removal were reported. RESULTS: Preoperative median IOP was 25.0 (20.5-30.3) mmHg in PStent and 25.0 (19.3-32.0) mmHg in PTrad (p = 0.62). One week after surgery, the median IOP dropped to 10.0 (8.0-13.0) mmHg in PStent and 7.0 (5.0-9.0) in PTrad (p < 0.01). At one month, the IOP was 12.0 (10.0-14.0) mmHg in PStent and 10.0 (8.0-11.0) mmHg in PTrad (p < 0.01). After 3 months, both groups showed similar median IOP levels of 11.0 (8.0-13.5) mmHg and 10.0 (9.75-13.0) mmHg in PStent and PTrad, respectively (p = 0.66). The presence of adverse hypotony was significantly lower in PStent compared to PTrad (6.2% vs 15.8%, p < 0.05). In PStent the stent was removed after 30.0 (21.0-42.5) days. One week after stent removal the mean IOP drop was 6.1 ± 0.5 mmHg (p < 0.01). CONCLUSION: In the early follow-up period, intraluminal stenting of the PMS appears to be safe and effective in controlling the IOP while reducing early postoperative hypotony. Surgical success is not compromised by stent placement. Based on our data, it is recommended to remove the suture two to six weeks after surgery for most patients with uncomplicated postoperative clinical findings.

Soluble B-cell maturation antigen in lacrimal fluid as a potential biomarker and mediator of keratopathy in multiple myeloma.

Belantamab mafodotin (belantamab) is a first-in-class anti-BCMA antibody-drug conjugate approved for the treatment of triple-class refractory multiple myeloma. It provides a unique therapeutic option for patients ineligible for CAR-T and bispecific antibody therapy, and/or patients progressing on anti-CD38 treatment where CAR-T and bispecifics might be kept in reserve. Wider use of the drug can be challenged by its distinct ocular side effect profile, including corneal microcysts and keratopathy. While dose reduction has been the most effective way to reduce these toxicities, the underlying mechanism of this BCMA off-target effect remains to be characterized. In this study, we provide the first evidence for soluble BCMA (sBCMA) in lacrimal fluid and report on its correlation with tumor burden in myeloma patients. We confirm that corneal cells do not express BCMA, and show that sBCMA-belantamab complexes may rather be internalized by corneal epithelial cells through receptor-ligand independent pinocytosis. Using an hTcEpi corneal cell-line model, we show that the pinocytosis inhibitor EIPA significantly reduces belantamab-specific cell killing. As a proof of concept, we provide detailed patient profiles demonstrating that, after belantamab-induced cell killing, sBCMA is released into circulation, followed by a delayed increase of sBCMA in the tear fluid and subsequent onset of keratopathy. Based on the proposed mechanism, pinocytosis-induced keratopathy can be prevented by lowering the entry of sBCMA into the lacrimal fluid. Future therapeutic concepts may therefore consist of belantamab-free debulking therapy prior to belantamab consolidation and/or concomitant use of gamma-secretase inhibition as currently evaluated for belantamab and nirogacestat in ongoing studies.

VEGF-A-induced changes in distal outflow tract structure and function.

PURPOSE: To investigate changes in distal outflow tract vessels caused by VEGF-A and their impact on outflow. METHODS: We compared VEGF-A perfused porcine anterior segments with and without trabecular meshwork (TM) to control eyes. In the first experiment (n=48), we analyzed live changes of the outflow tract with spectral-domain optical coherence tomography (SD-OCT) over 3 h and reconstructed them in 3D. In a second experiment (n=32), we measured the intraocular pressure (IOP) variation in response to VEGF-A over 48 h and computed the outflow facility. RESULTS: VEGF-A increased the vessel volume of the distal outflow tract by 16.8±10.6% while control eyes remained unchanged (0.5±6.8%). Volume changes occurred within the first 100 min before plateauing at 140 min. VEGF-A enhanced the outflow facility in eyes without TM by 38.6±25.5% at 24 h as compared to controls (p<0.05). CONCLUSION: VEGF-A dilated vessels of the distal outflow tract and increased the outflow facility even after TM removal, pointing to a regulatory mechanism independent of proximal structures.

Standard anterior peritomy versus a small posterior incision for the implantation of the PRESERFLO microshunt.

PURPOSE: To compare two approaches for the implantation of the PRESERFLO microshunt: an anterior approach (A) with a 6-8-mm peritomy and a posterior approach (P) with a 3-mm incision. METHODS: We retrospectively analyzed 126 patients who received a PRESERFLO microshunt. We compared intraocular pressure (IOP), surgical time, medication count, and postoperative complications over nine months. RESULTS: The baseline IOP was similar in A (21.8 ± 8.5 mm Hg) and P (23.9 ± 8.1 mm Hg) (p = 0.08). Surgical duration was significantly shorter in P (10 ± 0.4 min) than in A (26 ± 0.8 min) (p < 0.001). Postoperative IOP levels were comparable in A (10.8 ± 5.9 mm Hg) and P (10.6 ± 4.5 mm Hg) at 30 days (p = 0.62) and throughout the study (all intra-group p-values > 0.08). The preoperative medication count was 3.2 ± 1.3 drops in A and 3.3 ± 1.0 drops in P (p = 0.4). Postoperative values were 0.2 ± 0.6 in A and 0.3 ± 0.7 in P at nine months. There were no significant differences in complications and surgical revisions between groups (p-values > 0.05). CONCLUSION: Both techniques achieved satisfactory IOP and medication count reductions and had similar safety profiles, but the posterior incision technique was 2.6 times faster than the anterior incision technique.

The Role of Preoperative Case Selection in the Training of Surgical Repair of Primary Rhegmatogenous Retinal Detachment.

Purpose: To analyse single-operation anatomical success (SOAS) of primary rhegmatogenous retinal detachment (RRD) repair by junior vitreoretinal surgeons guided by preoperative individual case selection by an experienced mentor vitreoretinal surgeon. Methods: Retrospective, single institute, observational study, included all patients who underwent standard pars plana vitrectomy (PPV) or combined encircling band (CB) and PPV and gas tamponade in the treatment of RRD from November 2021 to December 2022 were included. Preoperative selection for the surgery decision, whether standard PPV or combined CB & PPV was undertaken through the senior surgeon; according to the location and extensions of the RRD, number of retinal tears (RT) and lens status. We excluded patients with tractional retinal detachment, RD with proliferative vitreoretinopathy stage C, giant tears, trauma, previous scleral buckle, schisis RD and RD requiring silicone oil. The primary outcome measure was to evaluate the single-operation anatomic success (SOAS). Secondary outcome measures evaluated whether there was a statistical significant difference between both procedures. Results: Eighty-two eyes were included in the study. Forty-five eyes were selected for combined CB&PPV and 37 eyes for standard PPV. SOAS was achieved in 40 eyes (88.8%) in combined group and 35 eyes (94.5%) in standard PPV group. There was no statistically significant difference in the success rate between both operations, p = 0.65. Conclusion: Structured preoperative selection of standardized surgical techniques according to the degree of complexity of RD together with close supervision enables junior vitreoretinal surgeons in training to achieve re-attachment rates of more than 80% with both types of surgeries.

Coarsened Exact Matching of Excisional to Plasma-ablative Ab Interno Trabeculectomy.

Aim: To compare ab interno trabeculectomy by trabecular meshwork (TM) excision to plasma-mediated ablation in primary open-angle glaucoma (POAG) patients. Methods: Retrospectively collected data of TrabEx+ (TEx) (n = 56) and Trabectome (T) (n = 99) patients were compared by coarsened exact matching to reduce confounding and matched based on baseline intraocular pressure (IOP) and age. The primary outcomes were IOP and the number of glaucoma medications. Complications and the need for additional glaucoma surgery were assessed. Patients were followed for up to 1 year. Results: A total of 53 TEx could be matched to T. Baseline IOP was 16.5 ± 4.6 mm Hg in both; age was 73.7 ± 8.8 and 71.5 ± 9.9 years in TEx and T, respectively. TEx was taking more medications than T (p < 0.001). IOP was reduced to 14.8 ± 4.3 in TEx and to 13.4 ± 3.4 in T at 6 months, and to 14.9 ± 6.0 (p = 0.13) in TEx and to 14.1 ± 3.8 mm Hg (all p < 0.05) in T at 12 months. Medications were reduced at both 6 and 12 months (p < 0.05). No differences were seen between TEx and T at 6 and 12 months. In TEx, only one serious complication occurred, and two patients required further glaucoma surgery. Conclusion: Although both groups had a baseline IOP considered low for ab interno trabeculectomy, IOP and medications were reduced further at 6 and 12 months. IOP reduction did not reach significance in TEx at 12 months. The intergroup comparison did not reveal any significant differences. Both had a low complication rate. Clinical significance: This study investigated subtle differences between a plasma-ablative device, the T, and an excisional device, the TEx, by applying coarsened exact matching. IOP and medications were reduced in both groups at 6 and 12 months, although IOP reduction did not reach significance in TEx at 12 months. The intergroup comparison did not reveal any significant differences, with both devices having a low complication rate. How to cite this article: Dakroub M, Verma-Fuehring R, Strzalkowska A, et al. Coarsened Exact Matching of Excisional to Plasma-ablative Ab Interno Trabeculectomy. J Curr Glaucoma Pract 2023;17(1):9-14.

Long-Term Outcome of Corneal Collagen Crosslinking with Riboflavin and UV-A Irradiation for Keratoconus.

PURPOSE: To evaluate long-term outcomes of corneal collagen crosslinking (CXL) using riboflavin and UV-A irradiation and to determine when to repeat CXL. METHODS: In this retrospective consecutive interventional case series 131 eyes of 131 patients (95 male, 36 female, mean age 29.7 ± 11.4 years) between 2006 and 2016 received standard CXL (Dresden protocol, epithelium-off) for progressive keratoconus. Corrected distance visual acuity (CDVA) and corneal tomography (K1, K2, Kmax) were repeatedly recorded 1 year (n = 103 eyes) to 10 years (n = 44) postoperatively. Only one eye per patient was included. Paired t-test or Wilcoxon matched-pairs signed rank test was used for parametric and nonparametric data, respectively. RESULTS: 1-3 years preoperatively, median K2 significantly increased by 1.1 D (p < 0.001). Postoperatively, median K2 increased by 0.1 D after 1 year, then decreased over the remaining postoperative period by 0.85 D (p = 0.021). Kmax fluctuated without significant change. Median apical corneal thickness decreased by 16 µm (p = 0.012) after 5 years and then returned to preoperative values. Mean CDVA showed a significant improvement (decrease in logMAR 0.08 after 10 years, p = 0.010). CXL non-responders, defined by a postoperative increase in Kmax>2 D, increased from 16% after 5 to 33% after 10 years. Risk factors for non-response were young age, high astigmatism (>4.3 D), thin cornea (<480 µm), poor initial visual acuity (CDVA ≥0.3 D), and atopic dermatitis. 4 eyes were re-treated 3-4 years after first CXL without complications and keratoconus stabilized thereafter. CONCLUSIONS: CXL can slow or stop keratoconus progression. However, as the number of responders declines after 5 years, especially patients with risk factors may require re-treatment.

Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical trial.

BACKGROUND: Neovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options. METHODS: TIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 µg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms. DISCUSSION: The best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663750 ; EudraCT: 2020-004917-10.

Comparison of a second-generation trabecular bypass (iStent inject) to ab interno trabeculectomy (Trabectome) by exact matching.

PURPOSE: To achieve a highly balanced comparison of trabecular bypass stenting (IS2, iStent inject) with ab interno trabeculectomy (T, Trabectome) by exact matching. METHODS: Fifty-three IS2 eyes were matched to 3446 T eyes. Patients were matched using exact matching by baseline intraocular pressure (IOP), the number of glaucoma medications, and glaucoma type, and using nearest neighbor matching by age. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. RESULTS: A total of 78 eyes (39 in each group) could be matched as exact pairs with a baseline IOP of 18.3 ± 5.1 mmHg and glaucoma medications of 2.7 ± 1.2 in each. IOP in IS2 was reduced to 14.6 ± 4.2 mmHg at 3 months and in T to a minimum of 13.1 ± 3.2 mmHg at 1 month. In IS2, IOP began to rise again at 6 months, eventually exceeding baseline. At 24 months, IOP in IS2 was 18.8 ± 9.0 mmHg and in T 14.2 ± 3.5 mmHg. IS2 had a higher average IOP than T at all postoperative visits (p < 0.05 at 1, 12, 18 months). Glaucoma medications decreased to 2.0 ± 1.5 in IS2 and to 1.5 ± 1.4 in T. CONCLUSION: T resulted in a larger and sustained IOP reduction compared with IS2 where a rebound occurred after 6 months to slightly above preoperative values.

Application of subretinal fluid to close refractory full thickness macular holes: treatment strategies and primary outcome: APOSTEL study.

INTRODUCTION: Persisting macular holes (PMH) after surgical release of any epiretinal traction of the vitreous and adjacent membrane may rely on secondary firm adhesions between the retracted retina and adjacent retinal pigment epithelium. Secondary application of subretinal (SR)-fluid may release these adhesions followed by an anatomical closure. METHODS: Twelve surgeons applied in a consecutive case series SR-fluid in 41 eyes with PMH and reported retrospectively their initial surgical, anatomical and functional experience with this approach. RESULTS: The mean duration of the MH prior to SR-fluid application was 17 months (6-96 months). The mean age of the patients at the time of surgery was 72 years (54-88). The mean preoperative aperture diameter of the opening was 1212 µm (239-4344 µm), base diameter 649 µm (SD 320 µm). The mean preoperative BCVA prior to surgery was 0.1 (0.01-0.3). All patients (41/41) complained about reduced BCVA and a significant central scotoma (negative scotoma) in their central field of vision. The secondary closure rate for our PMH was 85.36% (35 out of 41 eyes) at 6 weeks after surgery. The postoperative BCVA improved to 0.22 (0.02-0.5). The application of SR-fluid was not associated with major intraoperative adverse effects. CONCLUSION: Remaining SR-adhesions may inhibit PMH closure. Their release by application of SR-fluid will lead to a fast and immediate anatomical closure in many cases without serious adverse events.

Combined vitrectomy, near-confluent panretinal endolaser, bevacizumab and cyclophotocoagulation for neovascular glaucoma - a retrospective interventional case series.

Background: Neovascular glaucoma (NVG) is a severe, potentially blinding disease and a therapeutic challenge. The purpose of this study was to evaluate the safety and efficacy of an integrative surgical approach to neovascular glaucoma. Methods: Retrospective analysis of a one-year follow-up of a consecutive interventional case series of NVG. Eyes underwent transscleral cyclophotocoagulation, pars plana vitrectomy, near-confluent panretinal photocoagulation, and intravitreal bevacizumab. Phakic eyes underwent concomitant cataract surgery. Best-corrected visual acuity (BCVA, logMAR), intraocular pressure (IOP, mmHg), number of glaucoma medication, visual analog pain scale (VAPS, 0-10) were recorded at baseline, and 1, 3, 6, and 12 months. Blind eyes were excluded. Results: Seventy-seven eyes of 77 patients (45 male, 32 female, mean age 73.6±12.2 years) were included. NVG underlying conditions included retinal vein occlusion (41.6%), proliferative diabetic retinopathy (35.1%), central retinal artery occlusion (19.5%), and ocular ischemic syndrome (3.9%). Mean IOP decreased postoperatively from 46.3±10.1 mmHg to 14.5±7.9 mmHg (p<0.001), glaucoma medication from 4.7±1.3 to 1.8±1.8 (p<0.001), and VAPS from 6.0±1.8 to 0. BCVA remained unchanged. Postoperative intraocular inflammation had resolved in all eyes at the one-month follow-up. 71.4% (55/77) eyes did not require additional major interventions during follow-up. Conclusions: A single, comprehensive surgery session lowered IOP significantly, reduced GMS, and controlled pain.

[Effect of Selective Retina Therapy (SRT) on the Inflammatory Microenvironment of the Subretinal Space]. / Einfluss der Selektiven Retinatherapie (SRT) auf inflammatorische Zellmediatoren des subretinalen Raums.

PURPOSE: To investigate the effect of Selective Retina Therapy (SRT) on inflammatory key factors such as complement factor-C3 (CC3), tumor growth factor-beta2 (TGF-ß2), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). MATERIALS AND METHODS: Porcine RPE-Bruch's membrane-choroid explants were irradiated with two SRT laser systems, SRTYLF and SRTYAG (Nd : YLF laser, wave length 527 nm, pulse duration 1.7 µs and Nd : YAG laser, wave length 532 nm, pulse duration 2.4 - 3 µs). Laser irradiation was performed on a spot size of 200 × 200 µm, 30 pulses, with a repetition rate of 100 Hz, and a radiant exposure of 140 (threshold RPE death) and 180 mJ/cm2 per pulse (above threshold RPE death). Explants were cultivated in modified Ussing chambers and culture viability was assessed by calcein-AM cell staining. Secretion of inflammatory factors was analyzed by ELISA. Protein expression of tissue explants was assessed by Western blot. RESULTS: Regeneration of RPE was observed after 4 days. One day after SRT with 140 mJ/cm2 per pulse the secretion of basal CC3 decreased in ELISA. Following 180 mJ/cm2 radiant exposure, the level of IFN-γ decreased at day 4. CONCLUSION: SRT does not induce the release of the pro-inflammatory factors analyzed in this in-vitro study.

Incidence of submacular haemorrhage (SMH) in Scotland: a Scottish Ophthalmic Surveillance Unit (SOSU) study.

PURPOSE: Submacular haemorrhage (SMH) is a cause of severe visual loss in neovascular age-related macular degeneration (nAMD). The incidence is uncertain and furthermore there is no widely used classification system nor agreed best practice. The aim of this national surveillance study was to identify the incidence, presenting features and clinical course of new fovea-involving submacular haemorrhage associated with nAMD. METHODS: A questionnaire was sent monthly to every ophthalmic specialist in Scotland over a 12-month period asking them to report all newly presenting patients with acute SMH secondary to nAMD of at least two disc diameters (DDs) in greatest linear diameter. A follow-up questionnaire was sent 6 months after initial presentation. Cases related to other causes were excluded. RESULTS: Twenty-nine cases were reported giving an incidence of 5.4 per million per annum (range 2-15). The mean age was 83 years (range 66-96) and females accounted for 17/29 (59%). Fifteen of the 29 cases (52%) had a past history of AMD, of which 7 had nAMD. Nineteen of the 29 cases (66%) presented within 7 days of onset and the majority had SMH of < 11 DD (20/29, 69%). Treatment options comprised the following: observation (n = 6, 21%), anti-VEGF alone (n = 6, 21%) or vitrectomy with co-application of tissue plasminogen activator (TPA), anti-VEGF and gas (n = 17, 58%). The vitrectomy group experienced the greatest change in vision from logMAR 1.89-1.50 (p = 0.374). Four of 20 (20%) cases with 6 months follow-up suffered a re-bleed at a mean time of 96 days. CONCLUSIONS: The incidence, clinical features and course of a consecutive national cohort of patients with SMH secondary to nAMD are presented.

Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy.

Purpose: To investigate the effect of selective retina therapy (SRT) on the release of AMD-relevant cell mediators, such as matrix metalloproteinases (MMPs), VEGF, and pigment epithelium derived factor (PEDF) using different laser spot sizes and densities. Methods: Porcine RPE-choroid explants were treated with a pulsed 532 nm Nd:YAG laser using (1) large spot sizes, (2) small spot sizes with a high-density (hd) treatment, and (3) small spot sizes with a low-density (ld) treatment. Explants were cultivated in modified Ussing chambers. RPE regeneration and RPE cell death were investigated by calcein-AM staining and immunofluorescence. The MMP release was examined via zymography and immunofluorescence. VEGF and PEDF secretion was analyzed by ELISA. Results: During pigment epithelium regeneration (PER), mitosis and RPE cell migration were observed. Four days after SRT (large spot size) the content of active MMP2 increased significantly (P < 0.01). Hd treatment with small spot sizes resulted also in an increase of active MMP2 (P < 0.05). In immunofluorescence explants showed a localized expression of MMP2 within the healing lesions after irradiation. The PEDF level increased significantly (P = 0.01) after SRT with large spot sizes. VEGF secretion decreased significantly (P < 0.05) following SRT with large spot sizes and with hd treatment of small spot sizes. Conclusions: SRT induces a cytokine profile, which may improve the flux across Bruch's membrane, slows down progression of early AMD by RPE regeneration, and inhibits the formation of choroidal neovascularization. The cytokine release depends on the size and density of applied laser spots.

Postoperative Tropheryma whipplei endophthalmitis - a case report highlighting the additive value of molecular testing.

Introduction.Tropheryma whipplei is the causative agent of Whipple's disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms. Case presentation. A 74-year-old Caucasian female presented with blurred vision in the right eye over a period of 1-2 months, accompanied by stinging pain and conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was hand motion in the affected eye. Ophthalmological examination showed typical signs of intraocular inflammation. Diagnostic and therapeutic pars plana vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin and amikacin was performed within hours of initial presentation. Both microscopic analysis and microbial cultures of the vitreous biopsy remained negative for bacteria and fungi. The postoperative antibiotic regime included intravenous administration of ceftriaxone in combination with topical tobramycin and ofloxacin. Due to the empirical therapy the inflammation ceased and the patient was discharged after 5 days with cefpodoxime orally and local antibiotic and steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the PCR product revealed a specific sequence of T. whipplei. Conclusion. In our patient, endophthalmitis was the first and only symptom of Morbus Whipple, while most patients with Whipple's disease suffer from severe gastrointestinal symptoms. 16S rDNA PCR should be considered for any intraocular infection when microscopy and standard culture methods remain negative.

Thinning of Inner Retinal Layers after Vitrectomy with Silicone Oil versus Gas Endotamponade in Eyes with Macula-Off Retinal Detachment.

PURPOSE: To evaluate retinal layer thickness with optical coherence tomography (OCT) in eyes with macula-off retinal detachment after silicone oil (SiO) or gas endotamponade. PROCEDURES: Cross-sectional study of 40 eyes with macula-off rhegmatogenous retinal detachment that underwent vitrectomy. 20 eyes received SiO tamponade and 20 matched eyes received gas. 33 healthy fellow eyes served as controls. Macular spectral domain OCT was performed with automated layer detection in the 5 inner subfields of the Early Treatment Diabetic Retinopathy Study (ETDRS) map. RESULTS: Comparing the SiO group with the gas group, the ganglion cell layer showed a significant thinning in all fields of the inner ring of the ETDRS map, the inner plexiform layer in the nasal, superior and temporal quadrants, and the outer plexiform layer in the nasal quadrant. CONCLUSIONS: Inner retinal layers in the fovea/parafovea were significantly thinner in the SiO group. Prospective studies are warranted to further elucidate possible retinal adverse effects of SiO tamponade.

Vision loss under silicone oil tamponade.

PURPOSE: We aimed to investigate frequency, time course and pathophysiology of vision loss in eyes with macula-on rhegmatogenous retinal detachment operated with vitrectomy and silicone oil tamponade. PATIENTS AND METHODS: Fifteen eyes of 15 patients who had been operated with 5,000 centistoke silicone oil between 2006 and 2014 were included in a retrospective case series. Examinations included logMAR best corrected visual acuity (BCVA), visual field testing (VF), spectral domain optical coherence tomography (OCT), electrophysiology, and fluorescein angiography. RESULTS: Vision loss was seen in eight (53 %) eyes of 15 patients with symptomatic central scotoma, which was confirmed by VF (5/6). Preoperative median BCVA of these patients was 0.15 (0.5 to 0), prior to oil removal 0.7 (1.0 to 0.5), and 6 weeks post oil removal 1.0 (1.5 to 0.2). BCVA recovered in five patients to a median of 0.15 (0.5 to 0.1), and it remained 1.0 in three (20 %) out of 15 eyes. OCT revealed significant thinning of the foveal and parafoveal combined nerve fiber, ganglion cell and inner plexiform layers in affected eyes (mean 58.3 µm +/-13, horizontal scan through fovea, 500 µm radius) compared to their healthy fellow eyes (mean 84.5 µm +/-12.3; p < 0.01, n = 6 patients, 12 eyes) and compared to eyes with no vision loss under silicone oil. CONCLUSIONS: We find persisting vision loss in three out of 15 patients treated for macula-on rhegmatogenous retinal detachment with silicone oil tamponade. Thinning of inner retinal layers possibly evoked by silicone oil tamponade might be a pathophysiological explanation for vision loss in these patients.

Compatibility of recombinant tissue plasminogen activator (rtPA) and aflibercept or ranibizumab coapplied for neovascular age-related macular degeneration with submacular haemorrhage.

BACKGROUND/AIMS: Subretinal coapplication of recombinant tissue plasminogen activator (rtPA) and vascular endothelial growth factor (VEGF)-antagonists is a new treatment option for age-related macular degeneration complicated by submacular haemorrhage. Here, we investigate the compatibility of rtPA and aflibercept or ranibizumab in vitro because intraoperatively, rtPA or rtPA-induced plasmin may cleave aflibercept or ranibizumab. METHODS: Aflibercept and ranibizumab, respectively, were incubated with rtPA or plasmin, separated in gel electrophoresis and stained with Coomassie or silver. The antiangiogenic activity of the VEGF-antagonists was quantified by VEGF-ELISA after incubation with the supernatant of primary porcine retinal pigment epithelium cell cultures. RESULTS: In electrophoresis, ranibizumab displayed no additional fragments when it was coapplied with rtPA or plasmin. Its VEGF-inhibiting efficacy remained unchanged in coapplication with rtPA with or without blood, or plasmin. rtPA did not cleave or functionally compromise aflibercept. When aflibercept was coapplied with plasmin, electrophoresis displayed additional bands in Coomassie (30 kDa, 27 kDa, 19 kDa, 15 kDa) and silver staining (31 kDa, 26 kDa, 21 kDa, 19 kDa, 15 kDa). While at a clinical dosage (800 µg/mL) VEGF was inhibited by aflibercept when coapplied with plasmin, at borderline concentrations (400 ng/mL) VEGF-binding ability of aflibercept was abolished. CONCLUSIONS: Ranibizumab is not cleaved or functionally compromised by rtPA or plasmin. Aflibercept is cleaved and its VEGF-binding ability is reduced when coapplied with plasmin. In clinical practice, rtPA and ranibizumab can be coapplied as a treatment for neovascular age-related macular degeneration with submacular haemorrhage while the antiangiogenic activity of aflibercept may be compromised when coapplied with rtPA in the presence of plasmin.

Hyperthermia-induced upregulation of vascular endothelial growth factor in retinal pigment epithelial cells is regulated by mitogen-activated protein kinases.

PURPOSE: Localized application of hyperthermia is a potential treatment for retinal diseases. Vascular endothelial growth factor (VEGF) derived from the retinal pigment epithelium (RPE) is implicated in a variety of retinal pathologies. As it has been recently shown that hyperthermia may induce VEGF in the RPE, the aim of this study was to investigate hyperthermia-induced VEGF secretion and the pathways of hyperthermal VEGF upregulation in the RPE. MATERIAL AND METHODS: The human RPE cell line (Arpe-19) was exposed to 40°, 42°, 45° and 50 °C for one, five and 15 min. Cell viability was evaluated using a trypan blue exclusion assay, VEGF secretion was evaluated by an enzyme-linked immunosorbent assay ELISA) and VEGF expression was investigated using a Western blot. Involvement of mitogen-activated protein kinase (MAPK) pathways (ERK1/2, JNK, p38) and transient receptor potential vanilloid (TRPV) channels on VEGF induction was investigated using commercially available inhibitors (U0126, SB203580, SP600125, ruthenium red). Expression and phosphorylation of MAPKs was investigated using a Western blot. RESULTS: Hyperthermia induces time- and temperature-dependent cell death in human RPE cells. VEGF expression and secretion is induced by hyperthermia in a time- and temperature-dependent manner mediated by p38 and to a lesser degree by JNK. TRPV channels seem to play a minor role in regulation of hyperthermia-induced VEGF secretion. CONCLUSIONS: Hyperthermia induces temperature-dependent secretion of VEGF in the RPE, which is mediated by p38 and, to a lesser extent, JNK. This may lead to undesired effects from hyperthermal treatment of retinal diseases.

The long-term course of functional and anatomical recovery after macular hole surgery.

PURPOSE: To investigate the long-term effect of macular hole surgery, foveal structure and the thickness of retinal layers were analyzed with spectral-domain optical coherence tomography (SD-OCT). The long-term postoperative course of macular thickness and best-corrected visual acuity (BCVA) were followed. METHODS: In a retrospective cohort study, SD-OCT scans were obtained from the horizontal midline in 51 eyes 54±20 months postoperatively and from 30 control eyes. Retinal layer thickness was measured with a manual segmentation procedure aided by a customized computer program. BCVA was followed and macular thickness was quantified over time with the time-domain (TD) OCT Fast Macular Thickness program for up to 91 months. RESULTS: Median foveal thickness between the outer plexiform and ganglion cell layers was greater than normal while that of the other retinal layers was normal. The median foveal shape remained slightly distorted. The postoperative decrease of central macular thickness toward normal values was delayed to 28 months postoperatively. Nasal macular thickness was decreased to normal at 6 months while superior, temporal, and inferior macular thickness was decreased to normal at 1 to 2 months postoperatively. Preoperative mean BCVA was 20/100±3 lines. Postoperatively, mean BCVA was 20/44±2 lines at 3 to 6 months, 20/40±2 lines at 1 year, 20/32±2 lines at 2 years, and 20/28±1 line after a mean follow-up period of 54±20 months. CONCLUSIONS: Long-term postoperatively, the median thickness of retinal layers remains slightly thickened between the outer plexiform and the ganglion cell layer. The process of gradual recovery may continue for several years after macular hole surgery.