Evaluation of phakic intraocular lens power calculation using the new Linz-Homburg-Castrop formula and comparison with four conventional methods.

PURPOSE: To evaluate the accuracy of phakic intraocular lens (pIOL) power calculation in a middle European patient cohort. SETTING: EyeLaser Clinic, Linz, Austria. DESIGN: Single-center single-surgeon retrospective consecutive case series. METHODS: Patients were included after uneventful pIOL surgery implanting 91 nontoric and toric Visian implantable collamer lens model V4c. Online Calculation and Ordering System (OCOS) software, JPhakic software, Olsen-Feingold formula, Holladay formula, and Linz-Homburg-Castrop (LHC) formula were compared. When possible, lens constants were optimized for the patient cohort. Data of single eye per patient were included. Outcome measures were mean absolute prediction error, median absolute prediction error, mean prediction error with SD, and median prediction error, as well as the percentage of eyes with an absolute prediction error within limits of 0.25 diopters (D), 0.5 D, 0.75 D, and 1.0 D. RESULTS: 91 eyes of 91 patients were assessed. After application of the Cochran Q test, the Olsen-Feingold formula achieved a significantly lower percentage of eyes within an absolute prediction error of 1.0 D than all other methods. CONCLUSIONS: In the patient cohort, OCOS software, JPhakic software, and Holladay and LHC formulas showed equal results and can be cross-checked. The LHC formula was not published before. A ready-to-use Excel sheet is available as an addendum.

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.

Development of a new tissue injector for subretinal transplantation of human embryonic stem cell derived retinal pigmented epithelium.

BACKGROUND: Subretinal cell transplantation is a challenging surgical maneuver. This paper describes the preliminary findings of a new tissue injector for subretinal implantation of an ultrathin non-absorbable substrate seeded with human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). METHODS: Ultrathin Parylene-C substrates measuring 3.5 mm × 6.0 mm seeded with hESC-RPE (implant referred to as CPCB-RPE1) were implanted into the subretinal space of 12 Yucatan minipigs. Animals were euthanized immediately after the procedure and underwent spectral domain optical coherence tomography (SD-OCT) and histological analysis to assess the subretinal placement of the implant. Evaluation of the hESC-RPE cells seeded on the substrate was carried out before and after implantation using standard cell counting techniques. RESULTS: The tissue injector delivered the CPCB-RPE1 implant through a 1.5 mm sclerotomy and a 1.0-1.5 mm retinectomy. SD-OCT scans and histological examination revealed that substrates were precisely placed in the subretinal space, and that the hESC-RPE cell monolayer continued to cover the surface of the substrate after the surgical procedure. CONCLUSION: This innovative tissue injector was able to efficiently deliver the implant in the subretinal space of Yucatan minipigs, preventing significant hESC-RPE cell loss, minimizing tissue trauma, surgical complications and postoperative inflammation.

VITRECTOMY FOR PERSISTENT MACULAR HOLES FOLLOWING OCRIPLASMIN INJECTION: A Comparative Multicenter Study.

PURPOSE: To determine functional and anatomical outcomes of pars plana vitrectomy for persistent full-thickness macular hole (MH) after intravitreal injection of ocriplasmin. METHODS: This is a multicenter retrospective interventional study of 37 eyes of 37 patients who underwent pars plana vitrectomy with internal limiting membrane peeling for persistent MH after ocriplasmin treatment between December 2013 and December 2015 and comparison with 35 eyes of 35 patients who were offered ocriplasmin injection but underwent pars plana vitrectomy alone without pharmacologic vitreolysis before surgery. In addition, 24 matched pairs (MH diameter at baseline ±5 µm) were analyzed. Clinical data such as visual acuity, intraoperative characteristics, and spectral domain optical coherence tomography images were reviewed. Main outcome measures were visual acuity and MH closure rate. RESULTS: After a mean follow-up period of 9 months, postoperative mean visual acuity showed no significant differences between ocriplasmin-treated eyes (logarithm of minimum angle of resolution 0.37 ± 0.26, Snellen 20/47) and eyes without ocriplasmin treatment (logarithm of minimum angle of resolution 0.39 ± 0.25; Snellen 20/49) (P > 0.9). After ocriplasmin injection, mean MH diameter enlarged from 217 ± 102 µm to 384 ± 239 µm (P < 0.001). Matched-pair analysis revealed no difference in gain of visual acuity between the first visit and the last follow-up (P = 0.29). Macular hole closure was observed in similar proportion in ocriplasmin-treated eyes (97%) and vitrectomy-only eyes (94%) (P > 0.5). CONLCUSION: Eyes with persistent MH after ocriplasmin injection showed significant visual improvement after pars plana vitrectomy. Matched-pair analysis revealed no statistical differences in functional and anatomical postoperative results comparing with eyes of similar MH diameter that proceeded directly to surgery without ocriplasmin pretreatment.

Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases.

Anti-angiogenic therapies using biological molecules that neutralize vascular endothelial growth factor-A (VEGF-A) have revolutionized treatment of retinal vascular diseases including age-related macular degeneration (AMD). This study reports preclinical assessment of a strategy to enhance anti-VEGF-A monotherapy efficacy by targeting both VEGF-A and angiopoietin-2 (ANG-2), a factor strongly upregulated in vitreous fluids of patients with retinal vascular disease and exerting some of its activities in concert with VEGF-A. Simultaneous VEGF-A and ANG-2 inhibition was found to reduce vessel lesion number, permeability, retinal edema, and neuron loss more effectively than either agent alone in a spontaneous choroidal neovascularization (CNV) model. We describe the generation of a bispecific domain-exchanged (crossed) monoclonal antibody (CrossMAb; RG7716) capable of binding, neutralizing, and depleting VEGF-A and ANG-2. RG7716 showed greater efficacy than anti-VEGF-A alone in a non-human primate laser-induced CNV model after intravitreal delivery. Modification of RG7716's FcRn and FcγR binding sites disabled the antibodies' Fc-mediated effector functions. This resulted in increased systemic, but not ocular, clearance. These properties make RG7716 a potential next-generation therapy for neovascular indications of the eye.

Vancomycin in infusion during vitrectomy in surgical treatment of acute postoperative and posttraumatic endophthalmitis.

BACKGROUND: Endophthalmitis is potentially devastating intraocular inflammation following eye trauma or surgery. We describe the visual outcomes and causative pathogens in acute bacterial postoperative and posttraumatic endophthalmitis treated with immediate pars plana vitrectomy (PPV) with Vancomycin dissolved in the infusion fluid. METHODS: Clinical records of consecutive 30 patients with postoperative endophthalmitis and 15 patients with posttraumatic endophthalmitis were evaluated. Vancomycin was administered constantly in the infusion fluid at the time of complete PPV. Cultures were prepared from anterior chamber paracentesis. The mean follow-up period was 13 months. RESULTS: The visual acuities were improved in 38 cases (84 %) and remained stable in seven cases (16 %). Median post-PPV visual acuity was 1.0 logMAR in a group with postoperative endophthalmitis and 1.3 logMAR in a group with posttraumatic endophthalmitis (p < 0.05). Twenty cases (44 %) were culture-positive (Staphylococcus, Streptococcus, Enterococcus and Bacillus spp). CONCLUSIONS: Early PPV with Vanomycin in infusion leads to vision improvement in patients with both posttraumatic and postoperative endophthalmitis. In our series of 45 cases culture was positive only in half of the cases.

Proteomic Analysis of Vitreous Humor in Retinal Vein Occlusion.

PURPOSE: To analyze the protein profile of human vitreous of untreated patients with retinal vein occlusion (RVO). METHODS: Sixty-eight vitreous humor (VH) samples (44 from patients with treatment naïve RVO, 24 controls with idiopathic floaters) were analyzed in this clinical-experimental study using capillary electrophoresis coupled to mass spectrometer and tandem mass spectrometry. To define potential candidate protein markers of RVO, proteomic analysis was performed on RVO patients (n = 30) and compared with controls (n = 16). To determine validity of potential biomarker candidates in RVO, receiver operating characteristic (ROC) was performed by using proteome data of independent RVO (n = 14) and control samples (n = 8). RESULTS: Ninety-four different proteins (736 tryptic peptides) could be identified. Sixteen proteins were found to be significant when comparing RVO and control samples (P = 1.43E-05 to 4.48E-02). Five proteins (Clusterin, Complement C3, Ig lambda-like polypeptide 5 (IGLL5), Opticin and Vitronectin), remained significant after using correction for multiple testing. These five proteins were also detected significant when comparing subgroups of RVO (central RVO, hemi-central RVO, branch RVO) to controls. Using independent samples ROC-Area under the curve was determined proving the validity of the results: Clusterin 0.884, Complement C3 0.955, IGLL5 1.000, Opticin 0.741, Vitronectin 0.786. In addition, validation through ELISA measurements was performed. CONCLUSION: The results of the study reveal that the proteomic composition of VH differed significantly between the patients with RVO and the controls. The proteins identified may serve as potential biomarkers for pathogenesis induced by RVO.

Subretinal implantation of a monolayer of human embryonic stem cell-derived retinal pigment epithelium: a feasibility and safety study in Yucatán minipigs.

PURPOSE: A subretinal implant termed CPCB-RPE1 is currently being developed to surgically replace dystrophic RPE in patients with dry age-related macular degeneration (AMD) and severe vision loss. CPCB-RPE1 is composed of a terminally differentiated, polarized human embryonic stem cell-derived RPE (hESC-RPE) monolayer pre-grown on a biocompatible, mesh-supported submicron parylene C membrane. The objective of the present delivery study was to assess the feasibility and 1-month safety of CPCB-RPE1 implantation in Yucatán minipigs, whose eyes are similar to human eyes in size and gross retinal anatomy. METHODS: This was a prospective, partially blinded, randomized study in 14 normal-sighted female Yucatán minipigs (aged 2 months, weighing 24-35 kg). Surgeons were blinded to the randomization codes and postoperative and post-mortem assessments were performed in a blinded manner. Eleven minipigs received CPCB-RPE1 while three control minipigs underwent sham surgery that generated subretinal blebs. All animals except two sham controls received combined local (Ozurdex™ dexamethasone intravitreal implant) and systemic (tacrolimus) immunosuppression or local immunosuppression alone. Correct placement of the CPCB-RPE1 implant was assessed by in vivo optical coherence tomography and post-mortem histology. hESC-RPE cells were identified using immunohistochemistry staining for TRA-1-85 (a human marker) and RPE65 (an RPE marker). As the study results of primary interest were nonnumerical no statistical analysis or tests were conducted. RESULTS: CPCB-RPE1 implants were reliably placed, without implant breakage, in the subretinal space of the minipig eye using surgical techniques similar to those that would be used in humans. Histologically, hESC-RPE cells were found to survive as an intact monolayer for 1 month based on immunohistochemistry staining for TRA-1-85 and RPE65. CONCLUSIONS: Although inconclusive regarding the necessity or benefit of systemic or local immunosuppression, our study demonstrates the feasibility and safety of CPCB-RPE1 subretinal implantation in a comparable animal model and provides an encouraging starting point for human studies.

Proteomics of vitreous in neovascular age-related macular degeneration.

Neovascular age-related macular degeneration (nAMD) has been described as a predominantly inflammatory and proangiogenic retino-choroidal disease. Vitreous humor (VH) is the adjacent and accessible compartment which, due to the vicinity to the retina, might best represent changes of protein-based mediators of nAMD. The aim of this clinical-experimental study was to analyze the nAMD associated VH proteome of previously untreated patients whilst taking different groups of nAMD into account, based on their clinical presentation (clinical diagnosis groups). Electrophoresis coupled online to mass spectrometry (CE-MS) as well as liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) were used to analyze VH of 108 nAMD patients and 24 controls with idiopathic floaters. A total of 101 different proteins with at least two unique peptides could be identified. Using a stringent statistical analysis with implementation of the closed test principle, we were able to identify four proteins that may be involved in the pathophysiology of nAMD: Clusterin, opticin, pigment epithelium-derived factor and prostaglandin-H2 d-isomerase. Using independent samples, ROC-Area under the curve was determined proving the validity of the results: Clusterin 0.747, opticin 0.656, pigment epithelium-derived factor 0.514, prostaglandin-H2 d-isomerase 0.712. In addition, validation through ELISA measurements was performed. The identified proteins may serve as potential biomarkers or even targets of therapy for nAMD.

Current treatment modalities in diabetic macular edema.

Diabetic macular edema is the major cause of vision impairment in the diabetic population. Its treatment requires a multidisciplinary approach and the use of both systemic and local therapies. Current management includes the vascular endothelial growth factor inhibitors and steroids administered as intravitreal injections, as well as laser therapy and surgical treatment. Treatment modalities in diabetic macular edema have changed in recent years, after the introduction of vascular endothelial growth factor inhibitors, which are gradually replacing laser photocoagulation. All anti-VEGF agents tested so far showed efficacy in the treatment of diabetic macular edema. Due to structural differences, the therapeutic efficacy of different anti-VEGF products varies. According to recent results, 2,0 mg of aflibercept is more effective than 0,3 mg of ranibizumab in patients with lower visual acuity at baseline. Additionally, its superiority was shown in reducing the number of required macular laser photocoagulation procedures. This article provides a comprehensive overview of available therapeutic modalities based on laser photocoagulation, anti-VEGF agents, steroid injections or surgical interventions, and discusses their efficacy in patients with diabetic macular edema.

Randomized Clinical Trial to Compare Micropulse Photocoagulation Versus Half-dose Verteporfin Photodynamic Therapy in the Treatment of Central Serous Chorioretinopathy.

BACKGROUND AND OBJECTIVE: To evaluate subthreshold diode-laser micropulse (SDM) versus half-dose verteporfin photodynamic therapy (hd-PDT) in central serous chorioretinopathy (CSC). PATIENTS AND METHODS: 62 eyes of 62 patients were prospectively followed for changes in fluorescein angiography (FA), fundus autofluorescence (FAF), central macular thickness (CMT), best-corrected visual acuity (BCVA), and contrast visual acuity (CVA) after SDM (n=20) or hdPDT (n=24). CSC observation served as control group (n=18). RESULTS: Both treatment groups (60% SDM vs. 66.7% hdPDT) showed significant improvement in reduction of leakage activity compared to the control group (37.5%) at 16 weeks. CMT decreased by 69.7 µm (SDM), 109.8 µm (hdPDT), and 89 µm (control). BCVA improved by +6.7 (SDM group), +8.5 (hdPDT), and +1.5 ETDRS letters (control). CVA was best improved in the hdPDT group. No secondary RPE alterations could be detected by FAF after any intervention. CONCLUSION: In comparison to the control group, hdPDT and SDM resulted in reduced leakage activity in FA and enhanced photopic and scotopic visual acuity in patients with CSC.

Clinical Outcomes After Implantation of a Trifocal Toric Intraocular Lens.

PURPOSE: To evaluate the visual, refractive, and contrast sensitivity outcomes, as well as the level of photic phenomena, after cataract surgery with implantation of a trifocal diffractive toric intraocular lens (IOL). METHODS: This prospective study included 56 eyes with corneal astigmatism of 1.00 diopters (D) or greater of 28 patients (age: 23 to 78 years) undergoing cataract surgery with implantation of the trifocal toric IOL AT LISA tri toric 939MP (Carl Zeiss Meditec, Jena, Germany). Monocular and binocular visual outcomes, refractive changes, contrast sensitivity, and photic phenomena perception (Halo & Glare Simulator; Eyeland-Design Network GmbH, Vreden, Germany) were evaluated at 3 months postoperatively. RESULTS: Mean 3-month postoperative monocular uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuities were 0.13±0.15, 0.08±0.15, and 0.13±0.18 logMAR, respectively. Binocular postoperative CDVA, DCIVA, and DCNVA values were 0.10 logMAR or better in all cases. A total of 88.2%, 88.2%, and 95.5% of eyes achieved binocular UDVA, UIVA, and UNVA values of 0.20 logMAR or better, respectively. Postoperative refractive cylinder was 0.50 D or less and 1.00 D or less in 78.6% and 98.2% of eyes, respectively. Photopic contrast sensitivity was significantly better than mesopic values for the spatial frequencies of 6 (P=.007), 12 (P=.005), and 18 cycles/degree (P=.011). Mean size and intensity of halos were 50.67±15.69 and 54.89±17.86, respectively. Mean glare size and intensity were 39.67±3.51 and 44.67±15.01, respectively. CONCLUSIONS: The evaluated trifocal diffractive toric IOL provides an effective restoration of the distance, intermediate, and near vision after cataract surgery with good levels of visual quality and minimal photic phenomena.

Intermediate and near visual acuity of an aspheric, bifocal, diffractive multifocal intraocular lens with +3.25 D near addition.

PURPOSE: To evaluate the clinical outcomes after cataract surgery with implantation of a new diffractive multifocal intraocular lens with a lower near addition. METHODS: A prospective multicenter clinical study including 44 eyes of 44 patients (age range: 43 to 82 years) that underwent cataract surgery with implantation of the Tecnis ZLB00 multifocal intraocular lens (Abbott Medical Optics, Santa Ana, CA). Changes in uncorrected and corrected distance, intermediate, and near visual acuity, and manifest refraction were evaluated during a 3-month follow-up. Additionally, patients were asked about photic phenomena and spectacle dependence. RESULTS: Postoperative spherical equivalent was within 0.50 and ± 1.00 diopters of emmetropia in 91.2% and 100% of eyes, respectively. Postoperative monocular uncorrected distance, near, and intermediate visual acuities were 0.10 logMAR (20/25 Snellen) or better in 82.5%, 86.5%, and 68.8% of eyes, respectively. All eyes achieved monocular corrected distance and near visual acuity of 0.10 logMAR (20/25 Snellen) or better. All patients reported to be satisfied with the outcomes of the surgery. Only 6 patients (13.6%) required the use of spectacles for some daily activities postoperatively, and 8 patients (18.2%) reported mild perception of halos. CONCLUSIONS: The introduction of low addition multifocal intraocular lenses follows a trend to increase intermediate visual acuity. Still, a near addition of +3.25 diopters reached satisfying near results and led to high patient satisfaction.

Bilateral Macular Roth Spots as a Manifestation of Subacute Endocarditis.

A 42-year-old man presented with a 2-day history of impaired vision in the right eye (OD). The best corrected visual acuity (BCVA) (LogMAR) was 1.1 for the right eye and 0.0 for the left eye (OS). Fundus examination revealed white-centered hemorrhages resembling Roth spots in both macular regions. The spectral-domain optical coherence tomography (SD-OCT) showed intraretinal pseudocysts and hyperreflective deposits in the areas corresponding to the Roth spots. Conducted blood tests revealed elevated D-dimer concentration, increased total number of neutrophils, high C-reactive protein concentration, and elevated erythrocyte sedimentation rate. Procalcitonin concentration, platelet count, and body temperature were within normal ranges. A blood culture was ordered and yielded Streptococcus mitis and intravenous antibiotics were started immediately. The patient started complaining of chest and left calf pain. The systemic examination revealed infective endocarditis accompanied by bicuspid aortic valve and paravalvular abscess formation. The patient underwent cardiac surgery with mechanical aortic valve implantation. After recovery, the patient's visual acuities improved fully. Control ophthalmic examination, including SD-OCT, showed no abnormalities.

Intravitreal functional plasminogen in eyes with branch retinal vein occlusion.

PURPOSE: To evaluate whether intravitreal functional plasminogen is elevated in eyes with branch retinal vein occlusion (BRVO) and to discover whether intravitreal plasminogen activities are correlated with the extent of blood-retina barrier (BRB) breakdown. METHODS: Our study is a prospective case series of 20 consecutive patients with BRVO and 10 consecutive patients serving as controls. Vitreous taps were extracted from the central vitreous body and plasminogen was functionally determined in an innovative, ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). Intravitreal VEGF levels were assayed to estimate BRB breakdown. RESULTS: Intravitreal functional plasminogen was detected in all analyzed samples (n = 30) and mean (±SD) plasminogen activities were found to be 0.97 ± 1.06%N (range: 0.03-3.9%N). Patients suffering from BRVO exhibited significantly higher intravitreal plasminogen (1.35 ± 1.11%N) in comparison with controls (0.20 ± 0.21%N, p < 0.001). Intravitreal VEGF concentrations in the BRVO group (576 ± 547 pg/ml) were significantly higher than these in controls (111 ± 120 pg/ml, p = 0.003). There was a significant correlation between intravitreal functional plasminogen and intravitreal VEGF levels (r = 0.519, p = 0.003). CONCLUSIONS: Intravitreal functional plasminogen is significantly elevated in eyes suffering from BRVO and correlates with the extent of BRB breakdown. The induction of posterior vitreous detachment by using intravitreally administered recombinant tissue plasminogen activator (enzymatic vitreolysis) should be explored in further investigations.

Profile of ocriplasmin and its potential in the treatment of vitreomacular adhesion.

The recent approval by the US Food and Drug Administration of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA), often associated with vitreomacular traction (VMT) and macular hole (MH), has brought new attention to the field of pharmacologic vitreolysis. The need for an enzyme to split the vitreomacular interface, which is formed by a strong adhesive interaction between the posterior vitreous cortex and the internal limiting membrane, historically stems from pediatric eye surgery. This review summarizes the different anatomic classifications of posterior vitreous detachment or anomalous posterior vitreous detachment and puts these in the context of clinical pathologies commonly observed in clinical practice of the vitreoretinal specialist, such as MH, VMT, age-related macular degeneration, and diabetic macular edema. We revisit the outcome of the Phase II studies that indicated ocriplasmin was a safe and effective treatment for selected cases of symptomatic VMA and MH. Release of VMA at day 28 was achieved by 26.5% of patients in the ocriplasmin group versus 10.1% in the placebo group (P<0.001). Interestingly, for MHs, the numbers were more remarkable. Predictive factors for successful ocriplasmin treatment were identified for VMT (VMA diameter smaller than 1,500 µm) and MH (smaller than 250 µm). In comparison with the highly predictable outcome after vitrectomy, the general success rate of ocriplasmin not under clinical trial conditions has not fully met expectations and needs to be proven in real-world clinical settings. The ocriplasmin data will be compared in the future with observational data on spontaneous VMA release, will help retina specialists make more accurate predictions, and will improve outcome rates.

Effects of core vitrectomy in the treatment of age-related macular degeneration.

PURPOSE: To investigate the clinical efficacy and safety of an additional core vitrectomy to the standard therapy in patients with exudative age-related macular degeneration (ARMD). METHODS: In this prospective, controlled, single-centre study, 50 eyes of 50 patients (mean age: 74.1 ± 7.1; median 74 (69/78)) with ARMD were enrolled and randomized 1:1 to group 1 - core vitrectomy additional to three times injections of ranibizumab (3x Rbz) and Group 2 - 3x Rbz (control). 1 16 of 25 eyes in Group 1(64%) and 12 of 25 (48%) in Group 2 had a posterior vitreous detachment (PVD) prior to start of the study. Changes in best-corrected visual acuity (BCVA) using ETDRS charts, central macular thickness and macular volume (OCT) as well as the rate of reinjection with an OCT-based pro renata (PRN) protocol were monitored prospectively over 48 weeks. Forty-seven eyes completed follow-up at week 48. RESULTS: In Group 1, 4 of 24 lost 1 line of BCVA (16.7%) and 3 of 24 lost 2 lines (12.5%), whereas 17 of 24 gained more than 1 line (70.8%) and improved in average by 9.8 letters. In Group 2, 3 of 23 remained stable and 20 of 23 gained more than or exactly 1 line (78.3%), resulting in 14.3 letters, with no loss of lines. Central macular thickness decreased by 85.58 µm (28.8%) in Group 1 and by 121.43 µm (32.68%) in Group 2 compared with baseline. In Group 1, four patients received three additional and two patients, two additional Rbz injections. In Group 2, three patients received three additional, three patients two and 12 patients one additional Rbz injections. This yielded in an average injection rate of 3.66 in Group 1 and 4.17 in Group 2 over 48 weeks. Posterior vitreous detachment (PVD) was identified in Group 1 in 16 of 24 (66.7%) and in Group 2 in 12 of 23 (52.2%) patients at baseline. At week 48, 6 of 8 (75%) of the patients in Group 1 with initial attached vitreous showed a vitreal detachment, whereas only 1 of 11 (9%) in Group 2 had a new occurred detachment of the vitreous. No systemic or ocular adverse events were noticed. CONCLUSION: An initial core vitrectomy combined with a conventional ranibizumab injection regimen for exudative AMD patients was safe and lead to similar functional results with less intravitreal ranibizumab injections over 48 weeks.

Intravitreal functional plasminogen is elevated in central retinal vein occlusion.

PURPOSE: To detect intravitreal functional plasminogen in vitreous samples of patients with recent onset of central retinal vein occlusion (CRVO) and to demonstrate significantly higher intravitreal plasminogen in CRVO patients in comparison to controls. METHODS: Prospective clinical case series of 13 consecutive patients with recent onset of CRVO scheduled for core pars plana vitrectomy and 10 consecutive patients undergoing standard pars plana vitrectomy for routine macular surgery or vitreal floater removal. In all 23 cases, vitreous taps were extracted from the central vitreous body, and plasminogen was functionally determined in a new ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). RESULTS: Plasminogen was detected in all analyzed samples (n = 23), and mean plasminogen was revealed to be 1.33 ± 1.73% (mean ± SD), with a range of 0.03-7.8%N. Patients with recent onset of CRVO exhibited significantly higher intravitreal plasminogen (2.19 ± 1.89%N) in comparison to controls (0.20 ± 0.21%N; p < 0.001, Mann-Whitney U test). CONCLUSION: Due to significantly increased intravitreal plasminogen in patients with recent onset of CRVO, intravitreally administered tissue plasminogen activator might be an option to induce posterior vitreous detachment (enzymatic vitreolysis) in CRVO patients.

In vivo detection of hESC-RPE cells via confocal near-infrared fundus reflectance.

BACKGROUND AND OBJECTIVE: To investigate whether the confocal near-infrared reflectance (NIR) imaging modality could detect the in vivo presence of retinal pigment epithelium cells derived from embryonic human stem cells (hESC-RPE) implanted into the subretinal space of the Royal College of Surgeons (RCS) rat. MATERIALS AND METHODS: Monthly NIR images were obtained from RCS rats implanted with either hESC-RPE seeded on a parylene membrane (n = 14) or parylene membrane without cells (n = 14). Two independent, masked investigators graded the images. Histology and immunohistochemistry were performed at different time points (150, 210, and 270 postnatal days of age). RESULTS: NIR images revealed that an average of 20.53% of the parylene membrane area was covered by hESC-RPE. RPE-65 and TRA-1-85 confirmed the presence of human-specific RPE cells in those animals. No areas corresponding to cells were found in the group implanted with membrane only. Intergrader agreement was high (r = 0.89-0.92). CONCLUSION: The NIR mode was suitable to detect the presence of hESC-RPE seeded on a membrane and implanted into the subretinal space of the RCS rat.

Combination therapy in diabetic macular oedema and retinal vein occlusion--past and present.

This paper summarizes the recent evidence for combined therapies in the intravitreal medical treatment of diabetic macular oedema or macular oedema, secondary to retinal vein occlusion. Since the introduction of anti-inflammatory or anti-VEGF drugs combined with or used alternatively to laser, visual acuity can be stabilized or improved in a significant number of patients. However, there is an ongoing debate regarding the safety, efficiency and economic concerns related to these intravitreal monotherapies because they warrant frequent repetition to maintain the clinical effect. In the literature, the combination of photolasercoagulation, intravitreal steroids or VEGF-inhibitors, or both, shows early compelling evidence that some patients may benefit from less retreatment compared to monotherapy. To provide a conceptual and perspective approach for a first-line combined therapy, this paper also summarizes own results of pilot interventional case series of a 1.5 cc core pars plana vitrectomy and intravitreal substitution with balanced salt solution (BSS), 1.25 mg bevacizumab and 8 mg triamcinolone.