Macular microhole and foveal red spot syndrome: a critical review of the literature.

PURPOSE: The purpose of this article is to review the literature on nomenclature, natural history, clinical features, diagnosis, management, and prognosis of both macular microhole (MMH) and foveal red spot syndrome (FRS). METHODS: A PubMed primary literature search (February 1, 2020) utilizing the terms macular microhole, foveal red spot syndrome, and outer retinal hole was conducted. All chosen articles were case reports or case series. Articles qualified for inclusion if they documented symptoms, imaging findings, or followed patients longitudinally. RESULTS: A total of 14 studies from 1988 to 2019 that evaluated either MMH, FRS, or both were included in the review. No comparative study between the two defects was found. Studies often used the terms FRS and MMH interchangeably to reference both partial- and full-thickness lesions of the macula. Spectral-domain optical coherence tomography (SD-OCT) was most frequently able to identify these lesions and revealed an absence of all neural retinal layers from the inner limiting membrane (ILM) to the retinal pigment epithelium (RPE) in the full-thickness lesions while the partial-thickness lesions most often involved the photoreceptor layer (PRL) and less frequently the external limiting membrane (ELM). OCT revealed that vitreomacular traction (VMT) was involved in the natural history of both FRS and MMH for a significant subset of patients. CONCLUSION: The terms MMH and FRS have been used interchangeably in the literature. Advances in OCT have revealed that MMHs and FRSs are distinct but sometimes overlapping entities. We suggest that MMH and FRS are similar entities defined as one or more sharply defined lesions in the fovea of the eye < 150 µm in size. MMHs are a full-thickness defect of the entire neuroretina at the center of the foveola while FRSs are partial-thickness lesions. Current literature suggests that there may be subtle differences in the pathogenesis, clinical features, and diagnosis between MMH and FRS; however, prognosis and management for both are favorable. Lastly, we suggest that the terms outer lamellar macular microholes and full-thickness macular microholes may be the more appropriate terminologies to refer to FRS and MMH, respectively.

[Closure of Persisting Full Thickness Macular Holes by Subretinal Fluid Application: Technical Approach and Surgical Considerations]. / Verschluss von persistierenden Makulalöchern durch subretinale Flüssigkeitsapplikation: technisches Vorgehen und chirurgische Überlegungen.

INTRODUCTION: Firm adhesions between the retina and adjacent retinal pigment epithelium (RPE) may prevent the closure of macular holes (MH) after chromovitrectomy. Controlled application of subretinal (SR) fluid with BSS may release these adhesions leading to closure of the retracted retina in large and or refractory macular holes. METHODS: For a standardized procedure, it is recommended to exclude residues of epiretinal membranes on the retinal surface preoperatively at OCT or intraoperatively by means of vital dyes. Intraoperatively, a perfluorocarbon (PFO) bubble is placed above the MH and lowers the infusion bottle of 20 mmHg. Subsequently, SR-fluid blebs are applied in the upper, temporal and inferior quadrants with a subretinal 41-gauge cannula. After removing decalin bubble, the SR-detachment is enlarged toward the foveal center. This is essential to achieve a complete detachment of the outer macular edges from the RPE. The MH can be closed by a temporary gas endotamponade. RESULTS: With a standardized procedure, the operation can be carried out safely and with minimal effort. Additional measures, such as care for bubble-free SR-fluid sands or machine assistance, were added. In a pilot study, experienced VR surgeons performed the SR-fluid application safely and without complications. The preoperative diameter of the MH was 1150 µm (651 - 2350 µm). The secondary closure rate for our PMH was 80.9%. CONCLUSION: SR-adhesions seem to have a previously unnoticed component in persistent macular holes. An SR-fluid application can be carried out quickly, safely and with minimal material effort. The initial results show a high secondary closure rate.

Application of glycerol as carbon source for continuous drinking water denitrification using microorganism from natural biomass.

The contamination of water resources by nitrate is a global problem. Indeed, traditional treatment technologies are not able to remove this ion from water. Alternatively, biological denitrification is a useful technique for natural water nitrate removal. This study aimed to evaluate the use of glycerol as a carbon source for drinking water nitrate removal via denitrification in a reactor using microorganisms from natural biomass. The experiment was carried out in a continuous fixed bed reactor using immobilised microorganisms from the vegetal Phyllostachys aurea. The tests were started in batch mode to provide cells growth and further immobilisation on the support. Then, the treatment experiments were accomplished in an up-flow continuous reactor. Ethanol was used as the primary carbon source, and it was gradually replaced by glycerol. The C:N (carbon to nitrogen) ratio and the hydraulic residence time (HRT) were evaluated. It was possible to remove 98.14% of nitrate using a C:N ratio and HRT of 3:1 and 1.51 days, respectively. The results have demonstrated that glycerol is a potential carbon source for denitrification in a continuous reactor using immobilised cells from natural biomass.

A new dye based on anthocyanins from the acai fruit (Euterpe oleracea) for chromovitrectomy in humans: clinical trial results.

PURPOSE: To test the applicability of the acai dye at a 25% concentration for identifying the posterior hyaloids and internal limiting membranes (ILMs) during pars plana vitrectomy (PPV) in human eyes with macular holes (MHs). METHODS: This study included 25 patients with chronic idiopathic MHs. The exclusion criteria included glaucoma, previous significant ocular conditions, and previous ocular surgeries except uncomplicated cataract. Ten surgeons performed 23-gauge four-port PPV, phacoemulsification, posterior hyaloid detachment, ILM peeling guided by dye staining, and perfluoropropane injection. The patients remained prone for 5 days postoperatively. The patients were evaluated postoperatively after 1, 30, and 180 days. The surgeons completed a questionnaire regarding the dye's staining abilities. RESULTS: The posterior hyaloids and ILMs stained purple in all eyes. The final best-corrected visual acuity improved significantly (p < 0.001) from preoperatively (1.37 ± 0.29) to 180 days postoperatively (1.05 ± 0.43). The MHs closed in 76% of eyes. CONCLUSION: The acai dye at a 25% concentration identified posterior hyaloids and ILMs during PPVs in humans. Dye toxicity was unlikely.

INTRAVITREAL ZIV-AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results.

PURPOSE: To evaluate the 52-week safety and efficacy of intravitreal ziv-aflibercept in patients with neovascular age-related macular degeneration. METHODS: All patients received three monthly intravitreal injections of 0.05 mL of ziv-aflibercept (1.25 mg) followed by a pro re nata regimen. The best-corrected visual acuity and spectral domain optical coherence tomography were obtained at baseline and monthly. Full-field and multifocal electroretinograms were obtained at baseline and 4, 13, 26, and 52 weeks. For some full-field electroretinography parameters, we calculated the differences between baseline and 52 weeks and then compared those differences between treated and untreated fellow eyes. RESULTS: Fifteen patients were included and 14 completed the 52-week follow-up. The mean best-corrected visual acuity improved from 0.95 ± 0.41 (20/200) at baseline to 0.75 ± 0.51 (20/125) logarithm of the minimum angle of resolution at 52 weeks (P = 0.0066). The baseline central retinal thickness decreased from 478.21 ± 153.48 µm to 304.43 ± 98.59 µm (P = 0.0004) at 52 weeks. Full-field electroretinography parameters used to assess retinal toxicity after intravitreal injections (rod response and oscillatory potentials) remained unchanged during follow-up. The average multifocal electroretinography macular response in 5° showed increased N1-P1 amplitude and decreased P1 implicit time (P < 0.05). One patient presented with intraocular inflammation after the seventh intravitreal procedure. CONCLUSION: The results suggested that intravitreal ziv-aflibercept might be safe and effective for treating neovascular age-related macular degeneration. More patients and a longer follow-up are needed to confirm the long-term outcomes of intravitreal ziv-aflibercept.

Mating system and pollen dispersal in Eugenia dysenterica (Myrtaceae) germplasm collection: tools for conservation and domestication.

Eugenia dysenterica DC. (Myrtaceae) is a perennial tree producing edible fruits and ornamental flowers of potential value widely distributed in Brazilian "Cerrados" (savannas), but available genetic resources and potential for future breeding programs must be evaluated. Here we evaluated the reproductive system and pollen-mediated gene flow in one generation of Eugenia dysenterica germplasm collection of Agronomy School, Federal University of Goiás (in Goiânia city, Central Brazil). We collected leaves from all adults from the germplasm collection (682 plants) and seeds (542) from 23 mother-trees. Genotypes were obtained for seven microsatellite loci. Genetic diversity was high and did not significantly differ between adults (H e = 0.777) and progeny arrays (H e = 0.617). Our results showed that E. dysenterica has an allogamous mating system in the germplasm collection (t m = 0.957), but with high and significant biparental inbreeding (t m - t s = 0.109). Because sibs are very close to each other, mating between closely related individuals is likely. Paternity correlation was also relatively high, indicating a 11.9 % probability that a randomly chosen pair of outcrossed progeny from the same array are full sibs. The maximum pollen dispersal distance (224 m), estimated using assignment test, corresponded to the boundaries of the orchard. We were able to assign the paternity to only 64 % of the 349 seeds analyzed, indicating potential pollen immigration to the germplasm collection. The variance effective population size estimated for one maternal family in the germplasm collection (N ev = 3.42) is very close to the theoretical maximum value for half-sibs (Nev = 4.0). Because E. dysenterica has a long life cycle and generation time, the maintenance of an effective population size of at least 100 in the germplasm collection is suggested, which can be achieved by maintaining a seed-trees number around 30 individuals.

Corneal angiogenesis modulation by cysteine cathepsins: In vitro and in vivo studies.

Corneal avascularization is essential for normal vision. Several antiangiogenic factors were identified in cornea such as endostatin and angiostatin. Cathepsin V, which is highly expressed in the cornea, can hydrolyze human plasminogen to release angiostatin fragments. Herein, we describe a detailed investigation of the expression profile of cathepsins B, L, S and V in the human cornea and the role of cysteine peptidases in modulating angiogenesis both in vitro and in vivo. We used various methodological tools for this purpose, including real-time PCR, SDS-PAGE, western blotting, catalytic activity assays, cellular assays and induction of corneal neovascularity in rabbit eyes. Human corneal enzymatic activity assays revealed the presence of cysteine proteases that were capable of processing endogenous corneal plasminogen to produce angiostatin-like fragments. Comparative real-time analysis of cathepsin B, L, S and V expression revealed that cathepsin V was the most highly expressed, followed by cathepsins L, B and S. However, cathepsin V depletion revealed that this enzyme is not the major cysteine protease responsible for plasminogen degradation under non-pathological conditions. Furthermore, western blotting analysis indicated that only cathepsins B and S were present in their enzymatically active forms. In vivo analysis of angiogenesis demonstrated that treatment with the cysteine peptidase inhibitor E64 caused a reduction in neovascularization. Taken together, our results show that human corneal cysteine proteases are critically involved in angiogenesis.

Geometry, penetration force, and cutting profile of different 23-gauge trocars systems for pars plana vitrectomy.

BACKGROUND: To investigate the geometry, penetration force, and cutting profile of 23-gauge trocar systems for pars plana vitrectomy based on their grinding methods in a standardized laboratory setting. METHODS: In this experimental study, Eleven different commercially available 23-gauge sclerotomy trocar systems were divided into 4 groups according to their needle grinding and deburring: "back" bevel, "spear" bevel, "lancet" bevel, and "spatula" bevel. The normative geometrical data of the trocar systems were systematically analyzed according to nomenclature ISO 7864 and ISO 9626. Force to penetrate a 0.4-mm thick polyurethane foil was measured by a Penetrometer, when the trocar needle was piercing, cutting, and sliding through the foil at different defined loading phases and plotted as a load-displacement diagram. Magnified images of the consecutive cut were taken under a microscope after the entire penetration through the foil. Three physicians used all trocar systems in a masked fashion on human sclera to evaluate the manual penetration force in 30° and 90°. RESULTS: The mean outer diameter of the trocar systems was 0.630 ± 0.009 mm, and the mean outer diameter of the trocars was 0.750 ± 0.013 mm. The mean point length was 3.11 ± 0.49 mm, and the mean length of the bevel was 1.46 ± 0.23 mm. The primary bevel angle was 10.75 ± 0.41°, and the secondary bevel angle was 65.9 ± 42.56°. The piercing forces of the back bevel and spear-pointed trocars/needles were at the same level (0.087 ± 0.028 N). The lancet-pointed needle had remarkable low piercing and cutting forces with 0.41 N (range, 0.35-0.47 N). The spatula bevel tip showed the highest penetration piercing force with 1.6 N (range, 1.59-1.73 N). The back bevel systems induced frequently triangular-shaped incisions, with two nearly rectangular cuts of short length. The spear bevels produced a regular characteristic linear cut. Especially, the lancet blade created straight cut with a linear wound apposition. Spatula trocar systems caused usually an arched accurate incision. The manual force to penetrate the human sclera in an angled and rectangular angle appeared in the surgeons hand lower with a back bevel, lancet, or spear tip, whereas higher with spatula bevel systems. CONCLUSION: Lancet and back bevel systems show less penetration force of inner needles than the spatula systems. The results of the penetration force experiments correlated well with the manual force on sclera.

Development and initial experience with a colored perfluorocarbon liquid for intraocular tamponade in vitreoretinal surgery.

PURPOSE: To present the development and initial experience of a novel colored perfluorocarbon liquid (PFCL) in vitreoretinal surgery. METHODS: This was an experimental laboratory study and prospective human interventional study. F6H8 (Fluoron GmbH) was colored by adding 0.3 g/L blue anthraquinone dye. Subsequently, 20% colored F6H8 was prepared by mixing with perfluorooctane or perfluorodecalin (Fluoron GmbH). The novel product is not yet FDA approved for human application. In the laboratory, the colored PFCL was covered with 1) uncolored PFCL, 2) BSS, and 3) silicone oil. Cell toxicity was evaluated in L929 mouse fibroblasts using a growth inhibition assay. Porcine ex vivo eyes were evaluated after vitrectomy followed by intravitreal and subretinal colored PFCL infusion. A pilot, prospective, noncomparative interventional study was conducted in patients with retinal detachment with proliferative vitreoretinopathy (PVR). RESULTS: The density of the colored PFLC mixture was 1.664 g/cm for perfluorooctane and 1.802 g/cm for perfluorodecalin. There was no relevant cell growth inhibition with any concentration of colored PFCL tested. Experiments in pigs revealed that infusion of the colored PFCL caused neither staining of the internal limiting membrane nor intravitreal residual droplets. In the prospective study, 9 eyes (75%) underwent surgery for rhegmatogenous retinal detachment with at least grade C PVR. The colored PFCL enabled retinal break examination and detection of residual intravitreal droplets in all surgeries. There was no case of separation or leakage of the dye from the PFCL solution that could have caused unwanted staining of the vitreous or epiretinal surface. CONCLUSION: The colored PFCL enabled intraoperative maneuvers such as endolaser use. In addition, removal of the colored PFCL was easily achieved at the end of surgery.

Investigation of the retinal biocompatibility of acid violet for chromovitrectomy.

PURPOSE: The primary objective was to investigate the retinal biocompatibility of acid violet (AV) as a vital dye for chromovitrectomy. The secondary objective was to evaluate the capacity of AV to stain the anterior capsule of the lens. METHODS: An amount of 0.05 ml of 0.25 g/l and 0.5 g/l AV was injected intravitreally in the OD, while balanced salt solution (BSS) was applied in the OS for control. Clinical examination and histology with light microscopy (LM) were performed after 7 days. Retinal cell layers were evaluated for morphologic alterations and number of cells. The electroretinographic (ERG) changes were assessed at baseline and 7 days. In another part of the study, 0.1 ml of 0.25 g/l AV was injected into the anterior chamber of ex-vivo porcine eyes, and its capacity to stain the anterior capsule was determined. Cadaveric eyes were used to test the capacity of AV to stain the internal limitant membrane (ILM) during vitrectomy. RESULTS: The gross histopathologic appearance of the retina, choroids, sclera, and optic nerve was within normal limits, without any signs of severe retinal necrosis or cystic degeneration. AV caused no substantial retinal alterations in retinal layers by LM at either the lower or higher dose when compared with the control eye. The injection of AV did not induce considerable ERG alterations. The violet dye stained the anterior capsule after anterior chamber injection and the ILM, allowing a safer capsulorrhexis and vitrectomy. CONCLUSION: Acid violet may be safe for the retina at concentrations of 0.25 and 0.50 g/l after intravitreous injection, and may be used as a vital dye for staining the anterior capsule and the ILM.

Effect of vital dyes on retinal pigmented epithelial cell viability and apoptosis: implications for chromovitrectomy.

PURPOSE: To investigate the in vitro effect of vital dyes on toxicity and apoptosis in a human retinal pigment epithelial cell line. METHODS: ARPE-19 cells were exposed to brilliant blue (BBG), Evans Blue (EB), bromophenol blue (BroB), indocyanine green (ICG), infracyanine green (IfCG), light green (LG), fast green (FG), indigo carmine (IC) and Congo red (CR). Balanced salt solution was used as the control. Five different concentrations and 2 exposure times were tested. Cell viability was determined by the MTS (1-solution methyl thiazolyl tetrazolium) assay and apoptosis by Bax expression on Western blot. RESULTS: All dyes significantly reduced cell viability after 3 min of exposure at all concentrations (p < 0.01), except for BBG that was safe at concentrations up to 0.25 mg/ml and CR up to 0.05 mg/ml, while LG was safe at all concentrations. Toxicity was higher after 30 min of exposure. Expression of Bax was upregulated after all dye exposures, except BBG; ICG had the highest Bax expression (p < 0.01). CONCLUSIONS: Overall the safest dye was BBG followed by LG, IfCG, FG, CR, IC, BroB, EB and ICG. ICG was toxic at all concentrations and exposure times tested. Moreover, BBG was the only dye that did not induce apoptosis in ARPE-19 cells.

Staining properties of brilliant blue depending on different incubation times and solvents in humans.

PURPOSE: Intravitreous injection of vital dyes, e.g. brilliant blue (BBG), promotes better visualization of the internal limiting membrane (ILM). This paper investigates the staining properties of BBG depending on different incubation times and 2 types of solvents--5% glucose (GL) or saline solution--in a prospective study in patients. METHODS: This paper investigates various aspects of BBG in various methods. An interventional prospective study was conducted in patients to examine the binding properties of the blue dye diluted in either saline or 5% GL to epiretinal membranes (ERMs) and ILMs. Forty-nine consecutive patients older than 18 years scheduled for macular ERM, vitreomacular traction and macular hole surgeries were prospectively recruited. The primary outcomes of this study were the degree of ILM and ERM staining. The secondary outcomes of the study were the need of reinjection of BBG or any other dye, the ability of BBG to stain the vitreous, and frequency of complications. The staining of the ILM and ERM were graded as no staining, little, moderate or strong staining. RESULTS: There was no correlation between age (p = 0.32) or gender (p = 0.33) in the staining affinity of BBG to either the ILM or ERM. BBG may be an appropriate staining agent for the ILM in the majority (82%) of surgeries; however, in approximately half of the cases (45%) surgeons considered BBG not enough for ERM coloring and visualization. There is a tendency of BBG to stain the ILM better when saline solution is used compared to GL 5%; however, this was not statistically significant (p = 0.64). There was no difference in the staining efficacy of BBG to the ERMs by either solution (p = 0.70), despite the low staining affinity. CONCLUSION: BBG became the state-of-the-art dye for ILM identification. Differences in staining properties may imply that BBG should not be considered as first-line stain for ERM surgery. BBG is effective in ILM staining in over 80% of macular hole surgeries.

Biochemical analysis and decomposition products of indocyanine green in relation to solvents, dye concentrations and laser exposure.

PURPOSE: To investigate pH, ions, osmolarity and precipitation of indocyanine green (ICG), as well as the profile of ICG decomposition products (DPs) after laser exposure and the interaction with quenchers. METHODS: ICG was diluted in water, 5% glucose (GL) or balanced salt solution (BSS) to achieve concentrations of 2.5, 1, 0.25 and 0.1 mg/ml. Osmolarity, pH and precipitation were analyzed immediately and after 24 h. Precipitation analyses were done with a scanning electron microscope. Anion and iodate analyses of ICG and infracyanine green (IfCG) were performed by capillary zone electrophoresis. With regard to DPs, 0.5 mg/ml of ICG was assessed with high-performance liquid chromatography (HPLC) after 810-nm laser irradiation. DP profiles were evaluated with ICG dilution in quenchers (Trolox, histidine and DABCO) in 3 concentrations (0.1, 1 and 10 M). RESULTS: BSS promoted iso-osmotic ICG solutions of 208 mOsm (147-266) compared to GL with 177 mOsm. BSS solutions had a higher physiological pH of 7.2 compared with the GL one of 6.55. ICG precipitated more when diluted with BSS (5.95 mg); in contrast, GL showed less precipitate (3.6 mg). IfCG has no iodine derivates and other ICGs have an average 4.6% of iodate derivates. From HPLC analysis, 5 DPs were observed. The rate of DPs was higher when BSS was used (p < 0.05). Five DPs have been generated with ICG, and they may be altered with the quenchers DABCO, histidine and Trolox. CONCLUSIONS: BSS dilution induces more precipitation and DPs. ICG dilution in any solvent induces DPs. Quencher use reduces the amount of toxic DPs.

Evaluating Adherence to Diabetic Retinopathy Care in an Urban Ophthalmology Clinic Utilizing the Compliance With Annual Diabetic Eye Exams Survey.

Introduction The objective of this study was to identify barriers that affect adherence to the management of diabetic retinopathy (DR) in an urban ophthalmology clinic. Patient beliefs regarding diabetic eye care, transportation to the eye clinic, the COVID-19 pandemic, and treatment with panretinal photocoagulation (PRP) or anti-vascular endothelial growth factor (anti-VEGF) injections were investigated. Materials and methods The original Compliance with Annual Diabetic Eye Exams Survey (CADEES) included 44 statements designed with a 5-point Likert scale to assess patients' beliefs and understanding of their eye health and the importance of diabetic eye examinations. This survey was modified to include additional statements regarding the COVID-19 pandemic and free-response questions about transportation barriers and patients' subjective experiences with PRP or anti-VEGF injections. A total of 365 patients with a diagnosis of any stage of DR from SLUCare Ophthalmology were identified as potential participants to complete the telephone survey. Patients were classified as non-adherent if they did not have a dilated eye examination within the past year, missed a scheduled follow-up appointment for DR care within the past year, or missed an appointment for anti-VEGF injections or PRP. The mean Likert scores for each CADEES statement were compared between the adherent and non-adherent groups using independent samples t-tests. Demographics and clinical indicators were also reported and compared between the two groups. Results Out of 365 patients, 68 completed the modified CADEES. Twenty-nine patients were adherent, and 39 patients were non-adherent. Results from six of the 54 CADEES statements were significantly different between the adherent and non-adherent groups. These statements addressed patients' perception of their eye health, self-confidence in making an eye appointment, knowing someone with diabetic eye complications, self-confidence in controlling blood sugar, ability to use public transportation during the COVID-19 pandemic, and prioritizing eye health during the pandemic. There were no significant differences in clinical indicators or demographics between the adherent and non-adherent groups. Of the participants, 39.7% offered reasons for why transportation to the eye clinic was difficult. Patients suggested three novel reasons for missing eye appointments that were not specifically addressed in the CADEES. Fourteen unique barriers were reported for non-adherence with PRP or anti-VEGF injections. Conclusions The CADEES is a thorough tool for evaluating social barriers impacting adherence with DR appointments in an urban ophthalmology clinic. The survey did not identify any clinical or demographic risk factors for non-adherence in this patient population. Decreased patient self-efficacy may lead to non-adherence with the management of DR. The COVID-19 pandemic impacted the adherence of a small percentage of patients.

Surgical classification for large macular hole: based on different surgical techniques results: the CLOSE study group.

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.

Current concepts in vitreomacular traction syndrome.

PURPOSE OF REVIEW: As Reese first described the vitreomacular traction (VMT) syndrome in 1970, the knowledge base about the disease has been changing over time due to the advent of the high-definition optical coherence tomography (HD-OCT). The aim of this article was to present the current information on the pathophysiology, anatomic macular abnormality associations, treatments, and new concepts in VMT syndrome. RECENT FINDINGS: HD-OCT has provided unprecedented visualization of the vitreomacular interface, which has led to better comprehension of the VMT syndrome. The technologic advances also emphasized the need to review the basis of the VMT syndrome and define as yet unsettled and often confusing concepts. SUMMARY: The recognition of the role of VMT in a variety of macular conditions is imperative for proper diagnosis and appropriate management of these diseases.

Toxicity and retinal penetration of infliximab in primates.

PURPOSE: To evaluate the retinal penetration and toxicity of two doses of intravitreal infliximab in primates. METHODS: Ten marmosets (Callithrix jacchus) were given intravitreal injection of 100 µg or 400 µg of infliximab, and balanced salt solution served as control. At baseline and after 24 hours (5 animals) and 7 days (the other 5), the eyes were examined by electroretinography. They were then killed (at 24 hours and 7 days) and assessed by light microscopy and transmission electron microscopy for toxicity and immunohistochemistry, using a biotinylated anti-human immunoglobulin G, to evaluate retinal penetration. RESULTS: There was no difference over 50% of the electroretinography b-wave between baseline and the time points studied in all animals. Light and electron microscopy, and electroretinography analysis, showed no signs of toxicity in any of the animals. Strong presence of infliximab was observed in all retinal layers 7 days after intravitreal injection at both doses (100 and 400 µg). CONCLUSION: Infliximab at doses of 100 and 400 µg seemed to cause no damage to the retina 24 hours and 7 days after its intravitreal injection, and deeply penetrated all its layers, in primates. These results encourage future perspectives for the treatment of chronic inflammatory diseases of the retina in humans.

Use of lutein and zeaxanthin alone or combined with Brilliant Blue to identify intraocular structures intraoperatively.

PURPOSE: To determine whether a natural dye solution based on lutein and zeaxanthin alone or combined with Brilliant Blue stains and facilitates peeling of intraocular membranes in human eyes. METHODS: In this study of 60 cadaveric eyes, open-sky vitrectomy including posterior hyaloid detachment was performed. Different lutein and zeaxanthin concentrations (0.01-20%) were tested alone or combined with different Brilliant Blue concentrations (0.0125-0.025%) in the corneal endothelium, corneal epithelium, anterior and posterior capsule, vitreous cavity through the macula including the posterior hyaloid, and internal limiting membrane. The various dye solutions were in contact with the intraocular membranes for <1 minute and then were removed by mechanical aspiration or membrane peeling initiated and completed with intraocular forceps. The specimens were examined by light and electron transmission microscopy. RESULTS: Contact between lutein and zeaxanthin and the retinal, lens, and vitreous surface resulted in orange and greenish staining of the intraocular membranes, which facilitated surgical steps in all eyes. Lutein and zeaxanthin alone was useful for vitreous identification and lutein and zeaxanthin combined with Brilliant Blue had strong affinity for internal limiting membrane and anterior capsule. Light microscopy confirmed internal limiting membrane removal in all eyes tested. No dye solutions remained in the eyes after the membrane removal. CONCLUSION: A natural dye solution based on lutein and zeaxanthin alone or combined with Brilliant Blue efficiently stained the anterior capsule, vitreous, and internal limiting membrane in human cadaveric eyes and may be a useful tool for vitreoretinal or cataract surgery.