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.

Background The CLOSE study group proposes an updated surgical classification for large macular holes based on a systematic review of new treatments. Recently, many new techniques have been introduced to treat large full-thickness macular holes (FTMH); although the indications are not clear. An updated surgical classification is needed to help surgical decision-making. Methods We gathered published series by the CLOSE Study Group members and from literature search until June 2021. Techniques included: internal limiting membrane peeling (ILM peeling), ILM flaps, macular hydrodissection (macular hydro), human amniotic membrane graft (hAM), and autologous retinal transplantation (ART). Within each technique, chi-square test assessed association between the minimal linear diameter (MLD) (in µm) and closure rate; the postoperative best-corrected visual acuity (BCVA) gains were compared among groups. Results Data extraction included 31 published articles: total of 1135 eyes. Eyes were divided into the following groups: ILM peel (n: 683), ILM Flap (n: 233), macular hydrodissection (n: 64), hAM (n: 59), and ART (n: 96). The initial BCVA and size were heterogenous between the groups. ILM peel showed the best results in large FTMH ≤ 535 µm (closure rate 96.8%); adjusted mean BCVA: 0.49 (LogMAR) with a statistical difference among groups. Large FTMH between 535 and 799 µm: ILM flap technique showed better results (closure rate 99.0%); adjusted mean BCVA: 0.67(LogMAR); also with a statistical difference. For large FTMH ≥ 800 µm more invasive techniques are required. Use of hAM, macular hydrodissection and ART showed higher closure rates for this category (100%, 83.3% and 90.5% respectively), and adjusted mean BCVA varied from 0.76 to 0.89. Although there was no statistical difference between those techniques for this group due to the smaller number of cases. Conclusions The CLOSE study group demonstrated the potential usefulness of a new surgical classification for large FTMHs and propose OCT biomarkers for use in clinical practice and future research. This new classification demonstrated that Large (400–550 µm) and X-Large (550–800 µm) holes can be treated highly successfully with ILM peel and ILM flap techniques, respectively. Further studies are necessary for the larger FTMHs (XX-Large and Giant), using the CLOSE classification, in order to determine which technique is better suited for each hole size and characteristics.

Purpose microRNAs (miRNAs) mediate the pathological mechanisms of diabetic retinopathy. In this study, we compared miRNA expression profiles in the vitreous between patients with proliferative diabetic retinopathy (PDR) and patients with a macular hole as non-diabetic controls, and between PDR patients treated with anti-vascular endothelial growth factor (VEGF) therapy and untreated PDR patients. Methods Vitreous samples of non-diabetic and PDR patients were screened for miRNAs with quantitative polymerase chain reaction (qPCR) panels. miRNA candidates were validated in vitreous samples of a second, independent cohort. In addition, the effect of anti-VEGF therapy was investigated in the vitreous of a third study population consisting of PDR patients who had not received anti-VEGF therapy and PDR patients who had received preoperative anti-VEGF therapy. Results During screening, seven miRNAs were found to be significantly higher in the vitreous of PDR patients, whereas two miRNAs were found to be significantly lower compared with non-diabetic controls. Validating the expression of these miRNAs in a second cohort resulted in the identification of six miRNAs that were expressed at significantly higher rates in the vitreous of PDR patients: hsa-miR-20a-5p, hsa-miR-23b-3p, hsa-miR-142-3p, hsa-miR-185-5p, hsa-miR-326, and hsa-miR-362-5p. Among these six miRNAs, hsa-miR-23b-3p levels were lower in the anti-VEGF-treated group of PDR patients compared with untreated PDR patients. Conclusions In this study, we identified six miRNAs that are expressed more highly in PDR patients and one miRNA that is expressed at a lower levels in anti-VEGF-treated PDR patients. Translational Relevance miRNAs identified in the vitreous of PDR patients may improve our understanding of the mechanisms leading to PDR.

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. 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. 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. 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.

Purpose Traction exerted on the vitreous base during vitrectomy poses a risk for retinal tears. We aimed to quantify core vitreous traction during vitrectomy using spring return and pneumatic cutters. Methods Juvenile porcine vitreous was vacuum held in a vitreous bath while traction was measured using precision force gauge during vitrectomy. The parameters included were aspiration rate, cut-rate, cutter size, and machine types. Results An empirical probabilistic model was developed. The traction was proportional to the aspiration rate but insignificantly dependent on the cut-rate. The traction probability was inversely proportional to the exponential function of the traction (p < 0.05). The traction was < 0.003 N for 99% of the time using either 23- or 25-gauge cutters. Conclusion The tractions measured were considered similar to the causative forces of an iatrogenic retinal tear during a pars plana vitrectomy. The results provide a safety reference matrix of instrumental parameters during vitrectomy.

PURPOSE:To evaluate the agreement and predictability of ocriplasmin treatment effects among retinal experts (raters) by assessment of retinal imaging data of eyes treated for vitreomacular traction in nine different centers in Germany and Austria.METHODS:Retrospective cohort study. Combined confocal near-infrared scanning laser ophthalmoscopy and spectral-domain optical coherence tomography images (Spectralis® device, Heidelberg Engineering GmbH, Germany) from 136 eyes of 135 subjects were reviewed by 14 raters using an internet-based grading database and a standardized questionnaire. In addition to the images taken within 2 days prior to treatment, age, gender, and lens status were disclosed to the raters. Treatment success was defined as a complete cleavage of the posterior vitreous cortex at day 28±5. Main outcome was the agreement and predictability among raters for assessment of treatment success.RESULTS:Raters generally accepted starting ocriplasmin treatment (chance for treatment success ≥ 1%) in 22.4 to 69.1% (median 53.2%) of eyes (moderate intra- and interrater agreements with kappa-values of 0.6 and 0.48). The likelihood for a high potential treatment success (equal or higher than 25%) was judged by the raters in 43.4% to 86.0% (median 62.6%) of eyes (moderate intra- and fair interrater agreements with kappa-values of 0.56 and 0.22). Allocating eyes for high potential treatment success overall increased the odds by 3.07, with odds ratios of single raters up to 4.06 to 6.16.CONCLUSIONS:These results underscore the importance of training health care providers in the evaluation of retinal imaging data and also to define characteristic morphological features better in the presence of vitreoretinal interface diseases. The better results of single raters in the predictability of treatment success by the allocation of eyes in the high-potential group indicates the high relevance of the meticulous analysis of retinal images.

Department of Ophthalmology, University Medical Center Göttingen, Göttingen, Germany Artemis Eye Clinic, Dillenburg, Germany Internationale Innovative Augenchirurgie, Duesseldorf, Germany International Vision Correction Research Centre Network (IVCRC.net), Department of Ophthalmology, University of Heidelberg and Eyeclinics Ahaus-Raesfeld-Rheine, Dr. Gerl & Colleagues, Ahaus Lag, Germany Department of Ophthalmology, Ruprecht-Karls-University Heidelberg and Augenzentrum Nymphenburger Höfe/Augenklinik Herzog Carl Theodor, Munich, Germany

Purpose: To evaluate the impact of the vitreoretinal interface architecture, in specific the angle between the posterior vitreous cortex and the internal limiting membrane, on vitreomacular traction (VMT) resolution in eyes treated with intravitreally injected ocriplasmin (Jetrea).Methods: Retrospective, multicenter cohort study and exploratory data analysis. Spectral domain optical coherence tomography assessments were performed before scheduled ocriplasmin injections. General (age and sex) as well as ocular variables (lens status, presence of epiretinal membrane formations, horizontal diameter of VMT, central retinal thickness, and in particular various prespecified angles between the posterior vitreous cortex and internal limiting membrane) were analyzed to evaluate their impact on successful VMT resolution.Results: Fifty-nine eyes of 59 patients were included. Univariate analysis of age (odds ratio [OR]: 0.881; 95% CI: [0.812-0.955]; P = 0.0022) and lens status (OR: 11.03; 95% CI: [2.23-54.57]; P = 0.0033) had a significant impact on successful VMT resolution, whereas sex (OR: 0.668; 95% CI: [0.126-2.065]; P = 0.4906), epiretinal membrane formation (OR: 0.581; 95% CI: [0.168-2.006]; P = 0.3903), horizontal diameter of VMT (OR: 0.99930; 95% CI: [0.99825-1.00035]; P = 0.1886), and central retinal thickness (OR: 0.9985; 95% CI: [0.9934-1.00436]; P = 0.56) failed. The angle at 500 mm apart from the fovea centralis, irrespective if measured nasally (OR: 1.135; 95% CI: [1.013-1.272]; P = 0.0289) or temporally (OR: 1.099; 95% CI: [1.001-1.208]; P = 0.0485), showed a significant correlation with VMT resolution.Conclusion: The angle between the posterior vitreous cortex and the internal limiting membrane 500 mm apart from the fovea centralis correlates with VMT resolution and may be a clinically useful marker for selection of patients to be treated with ocriplasmin. This observation needs to be proven in a prospective confirmatory investigation.

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).

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.

PURPOSE:To evaluate intraocular pressure (IOP) changes during experimental vitrectomy and the efficacy of Constellation Vision System's IOP control (IOPc) feature in reestablishing baseline pressure.METHODS:Using a pressure transducer in freshly enucleated porcine eyes, a broad range of parameters (baseline pressures, aspiration levels, and cut rates) were tested with 23- and 25-gauge probes and IOPc turned ON versus OFF.RESULTS:IOPc turned ON was significantly more effective than IOPc turned OFF in controlling IOP drop and stabilizing pressure during vitrectomy using a wide range of baseline pressures (20-70 mmHg). The 23-gauge system consistently presented a reduced drop from baseline compared with the 25-gauge system. The overall average drop for the 23- and 25-gauge systems was 12.79 mmHg and 21.17 mmHg, respectively. Both gauge sizes reestablished baseline pressure approximately 1.6 seconds after the initial pressure drop generated at the beginning of aspiration. A peak of IOP (overshooting) was observed when the pressure was returning to baseline using both 23- and 25-gauge systems.CONCLUSION:Using IOPc feature turned ON, 23- and 25-gauge probes were effective in reestablishing and sustaining baseline infusion pressures, although 23-gauge probes showed less IOP fluctuation than did 25-gauge probes.

The goal of this study was to quantitatively assess retinal thickness using spectral domain optical coherence tomography (SD-OCT) after subretinal implantation of human embryonic stem cell-derived retinal pigment epithelium in a porcine model. The implant is called CPCB-RPE1 for the California Project to Cure Blindness-Retinal Pigment Epithelium 1. Data were derived from previous experiments on 14 minipigs that received either subretinal implantation of CPCB-RPE1 (n = 11) or subretinal bleb formation alone (sham; n = 3) using previously described methods and procedures (Brant Fernandes et al. Ophthalmic Surg Lasers Imaging Retina 47:342–51, 2016; Martynova et al. (2016) Koss et al. Graefes Arch Clin Exp Ophthalmol 254:1553–65, 2016; Hu et al. Ophthalmic Res 48:186–91, 2016; Martynova et al. ARVO Abstract 2016. SD-OCT retinal thickness (RT) and sublayer thickness over the implant were compared with topographically similar preimplantation regions as described previously Martynova et al. ARVO Abstract 2016. Imaging results were compared to postmortem histology using hematoxylin-eosin staining. RT overlying the CPCB-RPE1 postimplantation was not significantly different from preimplantation (308 ± 72 μm vs 292 ± 41 μm; p = 0.44). RT was not significantly different before and after implantation in any retinal sublayer at 1 month. Histology demonstrated grossly normal retinal anatomy as well as photoreceptor interdigitation with RPE.

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.

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.

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.

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.

PURPOSE:To analyze the levels of lysophosphatidic acids (LPAs) and autotaxin (ATX) in undiluted vitreous of untreated patients with retinal vein occlusion (RVO).METHODS:Sixty-four vitreous samples (40 RVO, 24 controls with idiopathic floaters) were analyzed in this retrospective case series using LC/MS for LPAs 16:0, 18:0, 18:1, 20:4, and ELISA kits or Luminex technology for ATX, angiopoetin-1 (ANG-1), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), pigment epithelium-derived factor (PEDF), and vascular endothelial growth factor (VEGF). LPA and ATX levels were correlated with the visual acuity, central macular thickness (CMT), average retinal thickness (AvT), vitreal cytokine levels and with each other.RESULTS:Levels of every LPA species tested and ATX were significantly increased in the vitreous fluid from all patients with RVO (total LPAs: 968.0 ± 842.3 nM; ATX: 2.5 ± 1.02 nM) compared with controls (total LPAs: 225.2 ± 292.8 nM, P < 0.0001; ATX: 1.9 ± 1.00 nM, P = 0.005). There were strong positive correlations between the vitreal levels of IL-6, IL-8, MCP-1, VEGF and LPAs.CONCLUSION:Levels of LPAs and ATX were positively correlated with proinflammatory cytokines and VEGF and might thus play an important role in the development of macular edema secondary to RVO.

Purpose: To assess quantitatively the natural course of the visual field (VF) loss in patients with retinitis pigmentosa (RP) during 2-year period of observation.Methods: VFs were obtained by semi-automated kinetic perimetry (SKP) during four examinations of 16 patients suffering from RP. Three stimulus conditions (V4e, III4e and I4e) with a constant stimulus angular velocity of 3 degrees/s were used to assess the hill of vision in both eyes of each patient. The area of each isopter was measured in square degrees and corrected for the individual reaction time (RT).Results: There were four patients with mild restriction of VF, six with ring scotomas and six with advanced concentric constrictions of VF. Only I4e isopter area decreased significantly from the first to the last session (p = 0.006), the difference was 154 deg(2) being 13% of initial isopter area. The difference was not significant for V4e and III4e isopters. RT values did not differ significantly between four sessions.Conclusions: Only I4e isopter's area was decreased significantly during two years of observation. SKP provides a method of assessment of progression of the VF loss in patients suffering from RP by measurement of the isopters' area over time.

PURPOSE. The purpose of this study was to demonstrate the efficacy of the digital fluoroscopy system (DFS) for the in vivo assessment of pharmacologically induced posterior vitreous detachment (PVD) and vitreous liquefaction in a rabbit model.METHODS. Twenty eyes from 10 New Zealand white rabbits were divided into 5 groups. In each group, one rabbit received an intravitreal injection of 2.0 U plasmin in the right eye and 0.5 U plasmin in the left eye. Intravitreal injection of 0.1 mL balanced salt solution (BSS) was given in the right eye, and no injection was given in the left eye of another rabbit used as a control. Intraocular fluid dynamics were assessed by the DFS, using a contrast agent in each group at different time intervals (6 hours, 12 hours, 1 day, 3 days, and 7 days). After rabbits were killed, both eyes were enucleated. Scanning electron microscopy was used to confirm the morphological alterations of the vitreoretinal interface as observed in the DFS.RESULTS. Complete PVD was observed after 12 hours with 2.0 U plasmin injection, whereas complete PVD was observed only after 3 days in eyes injected with 0.5 U plasmin. Eyes that received BSS injection or did not receive an injection failed to show complete PVD even after 7 days. Complete vitreous liquefaction was observed after 7 days with 2.0 U plasmin injection, but no eyes with 0.5 U plasmin or BSS injection showed complete liquefaction. We could clearly confirm the presence of PVD and the degree of vitreous liquefaction by using DFS.CONCLUSIONS. Digital fluoroscopy system appears to be a useful tool for the evaluation of pharmacological vitreolysis in rabbits with clear in vivo visualization of PVD and vitreous liquefaction.