[Lamellar macular holes-In the center of vitreomacular interface diseases : Pathophysiology, spontaneous courses and treatment concepts]. / Makulaschichtforamen ­ im Zentrum der vitreomakulären Grenzflächenerkrankungen : Pathophysiologie, Spontanverläufe und Therapiekonzepte.

BACKGROUND: A lamellar macular hole (LMH) is characterized by a distinct morphologic configuration and can be distinguished from related entities such as macular pseudohole (MPH) and epiretinal membrane with foveoschisis (ERM-FS) by clear morphologic features. PURPOSE: Based on current knowledge, the pathophysiologic function of LMH in the spectrum of vitreomacular interface diseases will be described and therapeutic concepts will be presented. METHODS: Current studies are supplemented by case reports to provide a schematic overview of the natural history and therapeutic concepts at the vitreomacular interface. RESULTS: The LMH is as a retrospective marker for pathologic posterior vitreous detachment in adult patients and may be interpreted as the pathophysiologic center of tractional maculopathies. Various vitreomacular pathologies can result in LMH: a detached vitreomacular traction, a spontaneously closed penetrating macular hole, or an epiretinal membrane with foveoschisis. Pathophysiologically, a degenerative, progressive loss of the architecture of the foveal muller cell cone may be the underlaying mechanism, resulting in the typical undermining of the hole edges and occasionally in a full thickness macular hole. The optimal timing and the appropriate surgical method are the focus of current clinical studies. CONCLUSION: The pathophysiology of LMH indicates a smooth transition of tractive maculopathies. These should be prospectively evaluated in order to develop evidence-based treatment strategies for LMH.

[Macular hole: Differential diagnosis, treatment options and new guideline recommendations]. / Makulaforamen: Differenzialdiagnose, Behandlungsoptionen und neue Leitlinienempfehlungen.

Full-thickness macular holes (FTMH) usually result in a pronounced reduction of visual acuity and represent one of the most frequent indications for retinal surgery. If diagnosed and treatment is initiated at an early stage, surgery has a high success rate with respect to both hole closure and improvement of visual acuity. Optical coherence tomography (OCT)-based staging and sizing enables an estimation of the surgical outcome. The differential diagnostic distinction from clinically similar disorders, such as lamellar macular holes, macular pseudoholes, and foveoschisis is clinically relevant as the pathogenesis, prognosis and treatment are significantly different. While vitrectomy with peeling of the inner limiting membrane (ILM) and gas tamponade is established as the standard treatment for FTMH, some aspects of treatment are handled differently between surgeons, such as the timing of surgery, the choice of endotamponade and the type and duration of postoperative positioning. For FTMH associated with vitreomacular traction, alternative treatment options in addition to vitrectomy include intravitreal ocriplasmin injection and pneumatic vitreolysis. The current clinical guidelines of the German ophthalmological societies summarize the evidence-based recommendations for diagnosis and treatment of FTMH.

Agujero macular idiopático bilateral simultáneo con cierre espontáneo de un lado / Simultaneous bilateral idiopathic macular hole with spontaneous one-sided closure

Introducción: El agujero macular idiopático se caracteriza como la pérdida central de la agudeza visual. La presentación bilateral se presenta con una frecuencia desde el 4,8 hasta el 30 por ciento y el cierre espontáneo para diámetros menores a 250 um es de 3,5 por ciento. Objetivo: Describir las formas de presentación y tratamientos alternativos en pacientes con agujero macular idiopático. Presentación de caso: Paciente mujer de 66 años sin antecedentes médicos que presenta un agujero macular idiopático bilateral y simultáneo. En el examen de tomografía de coherencia óptica del ojo derecho presentó 190 um y del ojo izquierdo 210 um. En el ojo izquierdo se le realizó intervención quirúrgica y en el ojo derecho presentó un cierre espontáneo con evolución favorable anatómica y funcional. Conclusiones: Los agujeros maculares idiopáticos se pueden presentar de manera bilateral. Las opciones terapéuticas y el manejo quirúrgico son algunas de las alternativas para su atención(AU)

Introduction: Idiopathic macular hole is characterized as central loss of visual acuity. Bilateral presentation occurs with a frequency from 4.8 percent to 30 percent and spontaneous closure for diameters less than 250 um is 3.5 percent. Objective: To describe the forms of presentation and alternative treatments in patients with idiopathic macular hole. Case presentation: We present a case of a 66-year-old female patient with no medical history presenting with a simultaneous bilateral idiopathic macular hole. Optical coherence tomography examination of the right eye showed 190 um and of the left eye 210 um. In the left eye she underwent surgical intervention and in the right eye she presented spontaneous closure with favorable anatomical and functional evolution. Conclusions: Idiopathic macular holes can present bilaterally and therapeutic options and surgical management are some of the alternatives for their care(AU)

NONSURGICAL RESOLUTION OF FULL-THICKNESS MACULAR HOLES WITHOUT VITREOMACULAR TRACTION.

BACKGROUND/PURPOSE: The purpose of this study was to report a case series of full-thickness macular holes without vitreomacular traction that resolved without surgery. METHODS: This study is a retrospective case series of 11 patients who demonstrated closure of full-thickness macular holes without surgical intervention. RESULTS: All full-thickness macular holes closed, with all patients having improvement in visual acuity. All but one of the cases had visual acuity better than 20/40 at last recorded visit. Most cases presented with associated epiretinal membrane (73%), cystoid changes (64%), defects <150 µ m (80%), and resolved within 2 months (91%). Topical anti-inflammatory drops were used in 7 of 11 cases, and dorzolamide was used in one case. CONCLUSION: Full-thickness macular holes can develop in eyes without the presence of vitreomacular traction. Topical therapy without vitrectomy may be particularly helpful in closure of full-thickness macular holes with associated cystoid macular edema. Holes with a lamellar hole component may spontaneously resolve as part of a retinal remodeling process.

Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial.

PURPOSE: To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human choroideremia (CHM)-encoding cDNA in CHM. DESIGN: Prospective, open-label, nonrandomized, dose-escalation, phase I/II clinical trial. PARTICIPANTS: Fifteen CHM patients (ages 20-57 years at dosing). METHODS: Patients received uniocular subfoveal injections of low-dose (up to 5 × 1010 vector genome [vg] per eye, n = 5) or high-dose (up to 1 × 1011 vg per eye, n = 10) of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human CHM-encoding cDNA (AAV2-hCHM). Patients were evaluated preoperatively and postoperatively for 2 years with ophthalmic examinations, multimodal retinal imaging, and psychophysical testing. MAIN OUTCOME MEASURES: Visual acuity, perimetry (10-2 protocol), spectral-domain OCT (SD-OCT), and short-wavelength fundus autofluorescence (SW-FAF). RESULTS: We detected no vector-related or systemic toxicities. Visual acuity returned to within 15 letters of baseline in all but 2 patients (1 developed acute foveal thinning, and 1 developed a macular hole); the rest showed no gross changes in foveal structure at 2 years. There were no significant differences between intervention and control eyes in mean light-adapted sensitivity by perimetry or in the lateral extent of retinal pigment epithelium relative preservation by SD-OCT and SW-FAF. Microperimetry showed nonsignificant (< 3 standard deviations of the intervisit variability) gains in sensitivity in some locations and participants in the intervention eye. There were no obvious dose-dependent relationships. CONCLUSIONS: Visual acuity was within 15 letters of baseline after the subfoveal AAV2-hCHM injections in 13 of 15 patients. Acute foveal thinning with unchanged perifoveal function in 1 patient and macular hole in 1 patient suggest foveal vulnerability to the subretinal injections. Longer observation intervals will help establish the significance of the minor differences in sensitivities and rate of disease progression observed between intervention and control eyes.

Treatment of Inflammatory Macular Hole: Case Series and Review of Literature.

PURPOSE: To present the success rate of nonsurgical management of full-thickness inflammatory macular hole (IMH). METHOD: Retrospective case series of five patients with IMH. RESULT: Five eyes from five patients with IMH enrolled in the current case series. All five eyes had successful closure with corticosteroid in the form of topical, periocular, or intravitreal injections. Systemic immunomodulatory treatment was employed for two patients, in addition to local therapy. For local therapy, one patient received topical eye drops, subtenon injection of corticosteroid, and intravitreal injection of combination of corticosteroid and anti-VEGF was performed in two patients. The closed macular hole reopened in one patient after two years, which required pars plana vitrectomy and anatomical and visual success achieved. CONCLUSION: Inflammatory macular holes can be closed with non-surgical interventions, although reopening may occur which requires surgery.

Recognising and managing retinal detachments.

Retinal detachments are a potentially sight-threatening ophthalmic emergency that may result in significant, irreversible vision loss. The risk of developing retinal detachment increases with advancing age, myopia and trauma. Pre-existing retinal degenerations can precipitate a pre-detachment symptomatic period of photopsia or floaters, allowing clinicians to intervene early and prevent detachments. Novel imaging techniques, such as spectral-domain optical coherence tomography, and well-established topographic modalities, such as B scan, can help to elucidate the type of detachment and any underlying causes, and help with surgical management. The overarching goal of treatment is to identify and seal all retinal holes, relieve vitreoretinal traction and prevent further recurrence. Prompt prophylactic retinopexy of retinal holes and tears is crucial in preventing retinal detachment, the main treatments of which are pars plana vitrectomy, tamponading agents and silicone scleral buckle.

MANAGEMENT OF RETINAL PIGMENT EPITHELIUM TEAR DURING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: This article aims to review current evidence on the development, diagnosis, and management of retinal pigment epithelium (RPE) tear during anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Literature searches were performed using MEDLINE/PubMed databases (cut-off date: August 2019). RESULTS: Three key recommendations were made based on existing literature and clinical experience: 1) Multimodal imaging with color fundus photography, optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence imaging, optical coherence tomography-angiography, and/or fluorescein angiography are recommended to diagnose RPE tear and assess risk factors. Retinal pigment epithelium tears can be graded by size and foveal involvement. 2) Patients at high risk of developing RPE tear should be monitored after each anti-VEGF injection. If risk factors worsen, it is not yet definitively known whether anti-VEGF administration should be more frequent, or alternatively stopped in such patients. Prospective research into high-risk characteristics is needed. 3) After RPE tear develops, anti-VEGF treatment should be continued in patients with active disease (as indicated by presence of intraretinal or subretinal fluid), although cessation of therapy should be considered in eyes with multilobular tears. CONCLUSION: Although evidence to support the assumption that anti-VEGF treatment contributes to development of RPE tear is not definitive, some data suggest this link.

OCRIPLASMIN FOR VITREOMACULAR TRACTION IN CLINICAL PRACTICE: The INJECT Study.

PURPOSE: Randomized clinical trials have demonstrated the safety and efficacy of ocriplasmin in patients with vitreomacular traction (VMT), including those with macular hole (MH). The INJECT study prospectively evaluated ocriplasmin in the setting of clinical practice. METHODS: INJECT was a Phase 4, multicenter, prospective observational study. Patients were followed up for 12 months. Assessments included nonsurgical VMT resolution, nonsurgical MH closure, best-corrected visual acuity, occurrence of vitrectomy, and adverse events. RESULTS: The efficacy population (N = 395) received an ocriplasmin injection and had optical coherence tomography-confirmed VMT at baseline. At Day 28, the rate of nonsurgical VMT resolution was 40.7% in the overall group, and the rate of nonsurgical MH closure was 36.0% in the VMT with MH group. At Month 12, the rate of ≥2-line best-corrected visual acuity gain (irrespective of vitrectomy) was 36.8% in the overall group and 59.6% in the VMT with MH group. The percentage of patients who underwent vitrectomy in the study eye was 29.1% in the overall group and 55.6% in the VMT with MH group. Photopsia (9.8%) and vitreous floaters (6.8%) were the most frequent adverse events. CONCLUSION: The INJECT study showed that ocriplasmin is effective in a clinical setting in patients with VMT, with or without MH. No new safety signals were identified from this large and surgeon-selected patient group, although the significant limitations of the study design without an image reading center and scheduled study visit timings should be noted.

COMBINED INTERNAL LIMITING MEMBRANE FLAP AND AUTOLOGOUS PLASMA CONCENTRATE TO CLOSE A LARGE TRAUMATIC MACULAR HOLE IN A PEDIATRIC PATIENT.

PURPOSE: To describe a case of a large, traumatic macular hole in a pediatric patient closed using an internal limiting membrane flap in combination with autologous plasma concentrate (APC). METHODS: Description of a surgical technique as performed in one patient. RESULTS: Successful macular hole closure and improvement in postoperative visual acuity were achieved in the patient in whom the technique was performed. CONCLUSION: The combined use of APC with the internal limiting membrane flap is advantageous because the APC acts to hold the internal limiting membrane in proper position and promotes the proliferation of glial cells through the presence of growth factors. This technique may be particularly advantageous in chronic or recalcitrant holes particularly in the setting of trauma.

Outcome of autologous platelet concentrate and gas tamponade compared to heavy silicone oil tamponade in persistent macular hole surgery.

PURPOSE: Persistence represents the major reason for failure of primary macular hole repair. A variety of surgical approaches are available for treating persistent macular holes. To compare clinical outcome of re-pars plana vitrectomy combined with autologous platelet concentrate and sulfur hexafluoride 20% gas tamponade with heavy silicone oil in persistent macular hole. METHODS: Records of 48 consecutive eyes with persistent macular holes which underwent re-pars plana vitrectomy with either heavy silicone oil (35 eyes, persistent macular-hole minimum linear diameter: 518.8 ± 171.1 µm) or autologous platelet concentrate and sulfur hexafluoride 20% (13 eyes, persistent macular hole-minimum linear diameter: 454.1 ± 211.3 µm) were reviewed retrospectively. All patients underwent measurements of anatomical persistent macular hole characteristics evaluated by optical coherence tomography and visual function. Cases in which anatomical success failed after first re-pars plana vitrectomy were treated with the other surgical techniques, comparable to a cross-over design. RESULTS: Persistent macular hole closure rate was 57.1% with autologous platelet concentrate and sulfur hexafluoride 20% and 45.7% with heavy silicone oil (p = 0.102). Functional results were comparable when persistent macular hole closure was achieved (p ⩾ 0.741), but significantly better for the autologous platelet concentrate with sulfur hexafluoride 20% group when persistent macular hole closure failed (p = 0.019). CONCLUSION: Re-pars plana vitrectomy combined with autologous platelet concentrate and sulfur hexafluoride 20% seems to achieve at least non-inferior persistent macular hole closure rates and comparable functional results when compared to heavy silicone oil, suggesting autologous platelet concentrate and sulfur hexafluoride 20% as a safe surgical alternative in persistent macular hole. Especially when persistent macular hole closure failed, autologous platelet concentrate with sulfur hexafluoride 20% seems to be superior regarding visual outcome.

Pediatric retinal damage due to soccer-ball-related injury: Results from the last decade.

OBJECTIVE: To outline the incidence of posterior segment injuries related to soccer-ball blunt trauma in children. METHODS: Retrospective search of the computerized hospital medical database between the years 2007 and 2017. All pediatric trauma cases were reviewed and cases with blunt trauma related to direct orbital/ocular hit from a soccer-ball were included. Cases were divided into two groups (non-severe and severe) based on the presence of sight-threatening findings on presentation (e.g. retinal tear, vitreous hemorrhage, retinal detachment, and macular edema). RESULTS: Out of 343 pediatric patients with relevant diagnoses, 14 (4.1%) were treated for injuries related to soccer-ball trauma. All patients were males at their early-to-mid teens (14.3 ± 2.1 years). The most common funduscopic finding was peripheral commotio retina (13, 93%). There was equal distribution between the two groups (seven each). Retinal injury in the severe group included retinal tear (3), vitreous hemorrhage (4), retinal detachment (1), and macular hole (1). Five patients in this group presented with visual acuity of 20/25 or better. Rate of external signs of injury were similar in both groups. CONCLUSION: Soccer-ball blunt trauma in children can cause significant posterior segment injuries regardless of the presence of external injury or ocular complaints. A thorough ocular exam is mandatory in all cases for the detection of vision-threatening retinal injuries.

FAILED LASER RETINOPEXY IN A PATIENT UNDERGOING PAZOPANIB THERAPY.

PURPOSE: To report a case of failed endolaser retinopexy in patient taking pazopanib and possible association with impaired retinal remodeling. METHODS: Case report. RESULTS: A 68-year-old man with a history of radiation-induced high-grade metastatic mediastinal leiomyosarcoma, on pazopanib 600 mg daily, presented with a superior retinal tear 2 months after initiating pazopanib. The patient was treated with pars plana vitrectomy and endolaser retinopexy without any immediate complications. One month postoperatively, the patient was found to have a new superior macula-sparing rhegmatogenous retinal detachment extending through the laser barricade nasally. A large proportion of the laser lesions in this area had notably remained chalk-white. The patient underwent pars plana vitrectomy with scleral buckling, and repeat endolaser retinopexy. Pazopanib therapy was stopped 1 week later in consultation with the oncology team and was reinitiated after the retina seemed stable under silicone oil for several weeks. The scars from the patient's repeat endolaser retinopexy remained pale white at his clinic visit 2 months after the procedure, and at that time, his initial laser scars had only just begun to darken with pigment. Four and a half months after the initial vitrectomy and endolaser retinopexy, and three and a half months after his repeat vitrectomy and endolaser retinopexy, all the patient's laser scars have developed increased pigment, and his retina remains completely flat under silicone oil tamponade. CONCLUSION: Pazopanib may have had an adverse effect on retinal wound healing after vitrectomy with endolaser retinopexy, leading to persistence of pale laser lesions many weeks after laser application. It is possible that this may have impaired the typical development of chorioretinal laser scar formation and led to subsequent retinal detachment.

HUMAN AMNIOTIC MEMBRANE TO TREAT MACULAR HOLES THAT FAILED TO CLOSE, SULFUR HEXAFLUORIDE ENDOTAMPONADE VERSUS AIR ENDOTAMPONADE: A Prospective Comparative Study.

BACKGROUND/PURPOSE: To determinate the efficacy of the human amniotic membrane plugs with sulfur hexafluoride versus human amniotic membrane plug with air as endotamponade to treat macular holes that failed to close after vitrectomy plus internal limiting membrane peeling. Multimodal imaging was focused to evaluate preoperative features and postoperative changes. METHODS: Prospective interventional comparative study. Twenty eyes of 20 patients affected with macular hole that failed to close were divided into 2 groups: 10 eyes received an amniotic membrane plug with 20% sulfur hexafluoride tamponade and 10 eyes received an amniotic membrane plug with air tamponade. All eyes were studied using multimodal advanced diagnostic tools, such as spectral-domain optical coherence tomography, optical coherence tomography angiography, microperimetry, and adaptive optics to investigate the postoperative results. RESULTS: In both groups, all macular holes were found successfully closed after 12 months. Mean preoperative best-corrected visual acuity was 20/400 in the SF6 group and 20/250 in air group. Final mean best-corrected visual acuity was 20/63 in both groups. The superficial capillary plexus, studied using optical coherence tomography angiography, showed a statistically significant difference between the treated and the fellow eyes. Adaptive optics images revealed the presence of a photoreceptor cell mosaic in the area of the amniotic membrane plug. CONCLUSION: The human amniotic membrane combined with air endotamponade demonstrated its effectiveness to seal macular holes that failed to close after vitrectomy plus internal limiting membrane peeling. Advanced multimodal diagnostic imaging helped us to better understand the modifications associated with the use of the amniotic membrane in these cases.

Two cases of diabetic macular edema complicated by an atypical macular hole.

BACKGROUND: Here we report two patients who developed an atypical macular hole (MH) during the treatment course for diabetic macular edema (DME). CASE PRESENTATIONS: Patient 1 was a 73-year-old male. Optical coherence tomography (OCT) revealed perifoveal retinoschisis (RS) in addition to cystoid macular edema and serous retinal detachment (SRD) in his left eye, and that an MH had developed during the clinical course. A convex surface was formed at the MH margin toward the vitreous cavity, and granular shadows were observed in the fluid cuff. Intraoperative findings revealed a thin epiretinal macular membrane (ERM) around the MH. Patient 2 was a 79-year-old male. Although the patient underwent pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) in both eyes, RS and a thin ERM in addition to SRD was observed in his left eye after surgery, and an MH developed during the clinical course. As in Patient 1, a convex surface was formed at the fluid cuff margin toward the vitreous cavity. CONCLUSIONS: Both patients had persistent DME, SRD, RS, and a thin ERM before the development of the MH. OCT revealed the formation of a convex surface at the MH margin toward the vitreous cavity, suggesting that the fragility of the layered structure of the retina combined with tangential retinal traction may have been involved in the atypical MH form.

AUTOLOGOUS BLOOD CLOT COVERING INSTEAD OF GAS TAMPONADE FOR MACULAR HOLES.

PURPOSE: This study evaluates the efficacy and usefulness of vitrectomy with internal limiting membrane peeling and autologous blood clot covering without gas tamponade in the treatment of macular holes (MHs). METHODS: All patients with a full-thickness MH with a minimum diameter of <600 µm and a base diameter of <1,200 µm underwent pars plana vitrectomy and internal limiting membrane peeling with autologous blood covering the MH at the end of the surgery. No fluid-air exchange or gas tamponade was performed. Postoperatively, all patients were instructed to adopt supine position overnight and thereafter any comfortable posture. RESULTS: A total of 18 eyes of 18 consecutive patients were included. The mean age of the patients (12 women and 6 men) was 59.06 ± 14.31 years (range, 21-81 years). The MHs composed of 13 idiopathic MHs, 2 MHs with high myopia (axial length > 26.5 mm), 2 traumatic MHs, and 1 MH associated with diabetic macular edema. Among them were five large MHs (minimum diameter > 400 µm). Complete MH closure was achieved in all eyes at the end of the follow-up period (range, 3-14 months). Visual acuity was significantly improved from preoperative 0.89 ± 0.41 logarithm of the minimum angle of resolution (20/155 Snellen) to 0.42 ± 0.33 logarithm of the minimum angle of resolution (20/53 Snellen) at the final visit (P < 0.001). CONCLUSION: The novel surgical protocol using vitrectomy, internal limiting membrane peeling, and autologous blood clot covering at the end of the MH surgery with limited diameters achieved highly effective closure and visual improvement and eliminated the gas tamponade and thus the associated adverse effects and the need for postoperative face-down positioning.

Prognostic Factors in Patients with Persistent Full-Thickness Idiopathic Macular Holes Treated with Re-Vitrectomy with Autologous Platelet Concentrate.

PURPOSE: To identify the predictors for anatomical and functional outcome after re-vitrectomy with application of autologous platelet concentrate (APC) in eyes with persistent idiopathic macular hole (MH). METHODS: Retrospective study of 103 eyes with persistent MHs after vitrectomy with peeling of internal limiting membrane (ILM) and expansive gas. All patients underwent re-vitrectomy with APC and endotamponade. The anatomical MH closure rate and postoperative best-corrected visual acuity (BCVA) were evaluated. Further, predictive factors influencing the success of the surgery were analyzed. RESULTS: Median BCVA (logMAR) before the surgery was 1.00 (interquartile range [IQR] 0.80-1.30) and the median of minimum diameter between hole edges was 508 µm (IQR 387-631). The final closure rate after re-vitrectomy with APC was 60.2% (62 of 103 eyes). The following predictors were identified to significantly influence the closure rate: tractional hole index (THI), axial length, time between first and second surgery, and the experience of the surgeon (p < 0.05). CONCLUSIONS: Re-vitrectomy with APC led to the closure of 60.2% of the persistent MHs. The closure rate negatively correlates with increasing axial length, time between the first and second surgery, and the decreased THI. Further, experienced surgeons (with a history of >100 pars plana vitrectomies with ILM peeling) had significantly higher closure rates.