[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.

Ultrastructural Details of Epiretinal Membrane Foveoschisis.

INTRODUCTION: The aim of this study was to describe differences in the vitreomacular interface (VMI) in idiopathic epiretinal membrane (ERM) foveoschisis compared to macular pseudohole (MPH) and lamellar macular hole (LMH). METHODS: We analysed surgically excised epiretinal material and internal limiting membrane (ILM) specimens obtained from 16 eyes of 16 patients with ERM foveoschisis (6 eyes), MPH (5 eyes), and LMH (5 eyes) during standard pars plana vitrectomy (PPV) with membrane peeling. The three entities were classified according to the newly introduced optical coherence tomography (OCT) terminology. Transmission electron microscopy (TEM) was used to describe the ultrastructural features. RESULTS: We found fibrocellular epiretinal tissues in all samples analysed. However, the cell and collagen composition of the VMI differed between groups. Eyes with ERM foveoschisis were characterized by a higher number of cells, multilayered membranes, and thick strands of vitreous collagen embedding the major cell types of myofibroblasts compared to MPH. Eyes with MPH also showed a predominance of myofibroblasts, but these were located directly on the ILM with no collagen between the cells and the ILM. Eyes with LMH showed a thick, multilayered epiretinal proliferation consisting mainly of non-tractional glial cells, corresponding to hypodense epiretinal proliferation on OCT. Eyes with ERM foveoschisis and MPH were more likely to have incomplete PVD compared to LMH in terms of posterior hyaloid status. DISCUSSION/CONCLUSION: Tractional ERMs in eyes with ERM foveoschisis and MPH differ in their ultrastructure. The main difference is in the amount and topographical distribution of vitreous collagen. However, the epiretinal cell types are predominantly myofibroblasts in both entities. This highlights the importance of distinguishing ERM foveoschisis from both MPH and LMH in terms of pathogenesis and surgical peeling procedures.

Risk of transient vision loss after intravitreal aflibercept using vial-prepared vs. the novel prefilled syringe formulation.

Purpose: To compare the risk of transient vision loss (TVL) probably attributable to a severe intraocular pressure spike after intravitreal aflibercept application using the novel prefilled syringe (PFS) vs. the established vial system (VS). Methods: Datasets of the intravitreal injection service of the Ludwig Maximilians-University Munich and the Technical University Munich, Germany, were screened for documentation of TVL after intravitreal injection of aflibercept. The observation period included two full months prior to the introduction of the novel PFS and two months afterwards. TVL was defined as loss of perception of hand motion for a duration of >30 s. Results: Over a period of four months, 1720 intravitreal injections of aflibercept were administered in 672 patients. There were 842 injections with the old VS, and 878 injections using the novel PFS. Using the VS, TVL was noted during two injections (0.24%) in two patients, as compared to 11 cases of TVL (1.25%) in 10 patients with the PFS (p = 0.015). Using the PFS, patients had a 5.3-fold risk of TVL as compared to the VS (OR: 5.33; 95% CI: 1.2-24.1; p = 0.0298). Conclusion: There was a more than five-fold risk of TVL using the novel pre-filled aflibercept syringe as compared to the established vial system. During informed consent, this risk should be discussed.

Scleral Thickness as a Risk Factor for Central Serous Chorioretinopathy and Pachychoroid Neovasculopathy.

In the pathophysiology of central serous chorioretinopathy (CSC), scleral changes inducing increased venous outflow resistance are hypothesized to be involved. This work aims to investigate anterior scleral thickness (AST) as a risk factor for pachychoroid disorders. A randomized prospective case-control study was performed at the Ludwig Maximilians University, Department of Ophthalmology. In patients with CSC or pachychoroid neovasculopathy (PNV) and in an age- and refraction-matched control group, swept source optical coherence tomography (SS-OCT) was used to measure anterior scleral thickness (AST). Subfoveal choroidal thickness (SFCT) was assessed using enhanced depth imaging OCT (EDI-OCT). In total, 46 eyes of 46 patients were included in this study, with 23 eyes in the CSC/PNV and 23 eyes in the control group. A significantly higher AST was found in the CSC/PNV compared with the control group (403.5 ± 68.6 (278 to 619) vs. 362.5 ± 62.6 (218 to 498) µm; p = 0.028). Moreover, the CSC/PNV group showed a higher SFCT (392.8 ± 92.8 (191-523) vs. 330.95 ± 116.5 (167-609) µm, p = 0.004). Compared with the age- and refraction-matched controls, patients with CSC and PNV showed a significantly thicker anterior sclera. Scleral thickness might contribute to the venous overload hypothesized to induce pachychoroid phenotypes.

Microstructural morphology and visual acuity outcome in eyes with epiretinal membrane before, during, and after membrane peeling in intraoperative optical coherence tomography assisted macular surgery.

AIM: To measure the difference of intraoperative central macular thickness (CMT) before, during, and after membrane peeling and investigate the influence of intraoperative macular stretching on postoperative best corrected visual acuity (BCVA) outcome and postoperative CMT development. METHODS: A total of 59 eyes of 59 patients who underwent vitreoretinal surgery for epiretinal membrane was analyzed. Videos with intraoperative optical coherence tomography (OCT) were recorded. Difference of intraoperative CMT before, during, and after peeling was measured. Pre- and postoperatively obtained BCVA and spectral-domain OCT images were analyzed. RESULTS: Mean age of the patients was 70±8.13y (range 46-86y). Mean baseline BCVA was 0.49±0.27 logMAR (range 0.1-1.3). Three and six months postoperatively the mean BCVA was 0.36±0.25 (P=0.01 vs baseline) and 0.38±0.35 (P=0.08 vs baseline) logMAR respectively. Mean stretch of the macula during surgery was 29% from baseline (range 2%-159%). Intraoperative findings of macular stretching did not correlate with visual acuity outcome within 6mo after surgery (r=-0.06, P=0.72). However, extent of macular stretching during surgery significantly correlated with less reduction of CMT at the fovea centralis (r=-0.43, P<0.01) and 1 mm nasal and temporal from the fovea (r=-0.37, P=0.02 and r=-0.50, P<0.01 respectively) 3mo postoperatively. CONCLUSION: The extent of retinal stretching during membrane peeling may predict the development of postoperative central retinal thickness, though there is no correlation with visual acuity development within the first 6mo postoperatively.

Long-Term Results of Adjunct Autologous Platelet-Rich Plasma in Lamellar Macular Hole Surgery Showing Lasting Restoration of Foveal Anatomy.

The aim of this study was to evaluate the long-time results of highly concentrated autologous platelet-rich plasma (PRP) used as an adjunct in lamellar macular hole (LMH) surgery. Nineteen eyes of nineteen patients with progressive LMH were enrolled in this interventional case series, on which 23/25-gauge pars plana vitrectomy was performed and 0.1 mL of highly concentrated autologous platelet-rich plasma was applied under air tamponade. Posterior vitreous detachment was induced, and the peeling of tractive epiretinal membranes, whenever present, was performed. In cases of phakic lens status, combined surgery was carried out. Postoperatively, all patients were instructed to remain in a supine position for the first two postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, and spectral domain optical coherence tomography (SD-OCT) were carried out preoperatively and at minimum 6 months (in median 12 months) postoperatively. Foveal configuration was postoperatively restored in 19 of 19 patients. Two patients who had not undergone ILM peeling showed a recurring defect at 6-month follow-up. Best-corrected visual acuity improved significantly from 0.29 ± 0.08 to 0.14 ± 0.13 logMAR (p = 0.028, Wilcoxon signed-rank test). Microperimetry remained unchanged (23.38 ± 2.53 preoperatively; 23.0 ± 2.49 dB postoperatively; p = 0.67). No patients experienced vision loss after surgery, and no significant intra- or postoperative complications were observed. Using PRP as an adjunct in macular hole surgery significantly improves morphological and functional outcomes. Additionally, it might be an effective prophylaxis to further progression and also the formation of a secondary full-thickness macular hole. The results of this study might contribute to a paradigm shift in macular hole surgery towards early intervention.

How should we report the foveal status in eyes with "macula-off" retinal detachment?

Whilst pre- and postoperative multimodal imaging technologies including optical coherence tomography (OCT) have investigated the morphological correlates of worsened visual outcomes in rhegmatogenous retinal detachment (RRD) with foveal involvement, the nomenclature has adhered to the traditional ophthalmoscopy-based and rather vague term "macula-off". This article appraises the current literature with regard to the preoperative assessment and nomenclature of the foveal status in macula involving retinal detachment (MIRD). A literature review of recent publications assessing functional or morphological outcomes in MIRD was conducted, using the search terms "fovea-off" or "macula-off". The search date was April 28th, 2021. Original studies in English language were included. Case reports, review articles or letters were excluded. Forty relevant articles (range of publication dates: July 29th, 2020 - April 18th, 2021) were reviewed to assess the diagnostic modalities used, morphological parameters assessed, and any specific nomenclature introduced to specify the extent of macular detachment. The results suggest widespread variability and inconsistencies with regard to the preoperative assessment, diagnostic modalities and nomenclature used to describe the foveal status in eyes with RRD termed "macula-off". The extent of macular detachment may be classified by a wide range of morphological parameters, including the height of foveal detachment and the ETDRS grid as overlay tool in OCT devices. There is a scientific and clinical need for an updated nomenclature for eyes with "macula-off" RRD. Preoperative OCT findings should be reported on a regular and standardized basis in order to establish a consensus how to report the foveal status in eyes with MIRD.

Retinal Vascular Occlusion after COVID-19 Vaccination: More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study.

BACKGROUND: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). METHODS: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June-31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case-control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. RESULTS: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA-1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case-control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60-1.45, p = 0.75) in connection with a vaccination within a 4-week window. CONCLUSIONS: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.

Progression of Pachychoroid Neovasculopathy into Aneurysmal Type 1 Choroidal Neovascularization or Polypoidal Choroidal Vasculopathy.

PURPOSE: To describe the progression of pachychoroid neovasculopathy (PNV) into pachychoroid aneurysmal type 1 choroidal neovascularization (PAT1)/polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective longitudinal cohort study. SUBJECTS: Patients diagnosed with PNV with a follow-up of ≥2 years. METHODS: Multimodal imaging, including OCT and fluorescein and indocyanine green angiography, was reviewed for the presence of choroidal neovascularization (CNV), aneurysms within/at the margins of the CNV, and subfoveal choroidal thickness (SFCT). MAIN OUTCOME MEASURES: Rate of PNV to PAT1/PCV conversion and risk factors thereof. RESULTS: In total, 37 eyes of 32 patients with PNV with a mean follow-up of 3.3 ± 1.1 years (range, 2.0-5.2) were included in the study. At PNV diagnosis, the mean age was 59.7 ± 8.7 years (range, 38.5-78.0 years) and mean SFCT was 357 ± 92 µm (185-589). During the follow-up, 5 (13.5%) eyes developed aneurysms after a mean 3.4 ± 0.8 years (2.3-4.2), defining PAT1/PCV. The risk of PAT1/PCV conversion was 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. A mean of 5.2 ± 4.0 to 7.9 ± 3.6 intravitreal anti-VEGF injections were given per year, resulting in a significant reduction of SFCT to 317 ± 104 µm (122-589) (P = 0.0007). The age at diagnosis of PNV was significantly lower in eyes that later went on to develop PAT1/PCV (54.0 ± 5.6 [45.9-60.5] vs. 61.2 ± 8.4 [38.5-78.0] years; P = 0.025). At the end of the follow-up, SFCT had on average decreased by -14.0% ± 17.6% (-55.9% to 23.1%) in the PNV group, whereas it had increased by mean 6.9% ± 4.4% (0.00%-10.8%) in the PAT1/PCV conversion group (P = 0.0025). CONCLUSIONS: PNV can develop aneurysms within its type 1 CNV, defining the conversion to PAT1/PCV. In this study, the conversion to PAT1/PCV was seen in 13.5% of eyes, resulting in Kaplan-Meier estimates of risk for conversion of 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. Younger age at diagnosis of PNV and sustained choroidal thickening despite anti-VEGF therapy might be risk factors for PNV to progress into PAT1/PCV.

Improving morphological outcome in lamellar macular hole surgery by using highly concentrated autologous platelet-rich plasma.

PURPOSE: To evaluate the use of highly concentrated autologous platelet-rich plasma (PRP) in lamellar macular hole (LMH) surgery with regard to function and morphology. METHODS: We included 12 eyes of 12 patients with progressive LMH in this interventional case series. After 23/25-gauge pars plana vitrectomy, 0.1ml highly concentrated autologous platelet-rich plasma was applied under air tamponade. Induction of posterior vitreous detachment and peeling of tractive epiretinal membranes were performed whenever present. Phacovitrectomy was undertaken in cases of phakic lens status. Postoperatively, all patients were instructed to rest in a supine position for the first two postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, spectral-domain optical coherence tomography (SD-OCT), and fundus photography were carried out preoperatively and 6 months postoperatively. RESULTS: Foveal configuration was restored in 10 of 12 patients (83.3%) at 6 months postoperatively. Two patients who had not undergone ILM peeling showed a recurring defect at 6-month follow-up. Best-corrected visual acuity improved significantly from 0.29 ± 0.08 to 0.14 ± 0.13 logMAR (Wilcoxon: p=0.028). Microperimetry remained unchanged (23.38 ± 2.53 preoperatively; 23.0 ± 2.49 dB postoperatively; p=0.67). No patient experienced vision loss after surgery, and no significant intra- or postoperative complications occurred. CONCLUSION: The application of PRP in the surgical therapy of LMH results in good morphological and functional outcomes. Additional peeling of the ILM seems to be mandatory when using PRP to prevent the recurrence of LMH. Strict postoperative supine positioning for 2 h avoids PRP dislocation. Larger sample sizes are needed to confirm the results.

Functional recovery after macula involving retinal detachment and its correlation with preoperative biomarkers in optical coherence tomography.

To introduce an ETDRS grid-based classification for macula involving retinal detachment (MIRD) with or without center (foveal) involvement and to identify biomarkers in preoperative optical coherence tomography (OCT) associated with a favorable postoperative functional outcome in eyes with center involving retinal detachment (CIRD). One hundred and two eyes of 102 consecutive patients (f/m: 35/67) with primary rhegmatogenous retinal detachment, preoperative evidence of MIRD (perifoveal involvement of ≤ 6.0 mm), and successful retinal surgery were included in this retrospective cohort study. Eyes were assigned to 5 grades of MIRD (G1-G5), based on the extent of detachment in the ETDRS grid. Eyes with a detached foveal status (CIRD) were assigned to G4 or G5. In CIRD, the following OCT biomarkers were quantified and correlated with mean BCVA (logMAR) at 3 months postsurgery, using univariate and multivariable regression models: grade of detachment, extent of intraretinal edema, height of foveal detachment, subretinal folds, and epiretinal membrane. Forty-one of 102 eyes (40.2%) presented with an attached foveal status, defined as either outer (G1: 11.8%) or inner (G2: 18.6%) macular involvement or fovea-threatening MIRD (G3: 9.8%). Sixty-one eyes (59.8%) showed CIRD (G4 or G5). Eyes with CIRD had significantly worse postoperative BCVA than eyes without foveal involvement (0.355 logMAR vs. 0.138 logMAR, p<0.001). If CIRD was limited to three outer ETDRS quadrants (G4), mean BCVA was better compared to CIRD involving all four ETDRS quadrants (G5) (0.254 logMAR vs. 0.522 logMAR, p<0.001). Reading ability (BCVA ≤ 0.4 logMAR) was restored in 97.6% of eyes with G1-G3 compared to 86.9% of eyes with G4 (p=0.072) and 52.4% of eyes with G5 (p<0.001). In multivariable regression analysis of eyes with CIRD, a lower grade of detachment (G4 vs. G5: p<0.05) and lower extent of cystoid edema (focal/none vs. wide: p<0.001) were both associated with better postoperative function. The functional outcome after MIRD may be worse in the presence of foveal involvement (CIRD), but a lower grade of detachment and the absence of intraretinal edema can predict a good recovery in spite of CIRD.