Yuji Itoh

Correlation Between Foveal Cone Outer Segment Tips Line and Visual Recovery After Epiretinal Membrane Surgery

PURPOSE To determine whether there is a significant correlation between the integrity of the foveal microstructures and the best-corrected visual acuity (BCVA) after pars plana vitrectomy for epiretinal membrane (ERM) removal. METHODS This was a retrospective, interventional case series. Forty-six eyes of 45 patients with an ERM underwent vitrectomy. The foveal area was examined by spectral-domain-optical coherence tomography (SD-OCT) preoperatively and postoperatively. The correlation between the length of the photoreceptor cone outer segment tips (COST) line defect, the inner segment/outer segment junction (IS/OS) line defect, the external limiting membrane (ELM) line defect, and the BCVA was determined. RESULTS The length of the COST line defect was significantly correlated with the BCVA at postoperative 1, 3, 6, 9, and 12 months (P < 0.001 for all). Forward stepwise regression analyses showed that the postoperative BCVA was significantly correlated with the length of COST line defect (P < 0.001) but not with the IS/OS line and ELM line defects for up to 6 months. The preoperative length of the COST line defect was significantly correlated with the postoperative BCVA at 12 months (P = 0.005), but the lengths of the IS/OS line defect and ELM line defect were not. The factor that best predicted the postoperative BCVA was the length of the preoperative COST line defect (P = 0.04) but not the preoperative BCVA (P = 0.69). CONCLUSIONS The recovery of the foveal COST line defect is correlated with the BCVA after ERM surgery. The length of the preoperative COST line defect can predict the potential foveal function. (ClinicalTrials.gov number, NCT01549249.).

Factors Associated With Persistent Subfoveal Fluid and Complete Macular Hole Closure in the PIONEER Study

PURPOSE To investigate preoperative and intraoperative factors associated with persistent subfoveal fluid in surgically closed macular holes (MHs). METHODS This was a prospective consecutive case series of eyes undergoing surgical repair for full-thickness MH in the PIONEER study, a prospective intraoperative optical coherence tomography (OCT) multisurgeon single-center study. Thirty-seven eyes (36 patients) with surgically closed MH were studied. Quantitative OCT analysis was performed including intraoperative MH area, volume, ellipsoid zone to retinal pigment epithelium (EZ-RPE) height, extent of subretinal hyporeflectivity (SRHR), and the amount of postoperative subfoveal fluid. RESULTS Persistent subfoveal fluid was identified in 58% of eyes at 2 weeks following surgery. The mean time to two-line improvement in visual acuity was greater in eyes with persistent subfoveal fluid (P = 0.03). Final visual acuity did not correlate with the initial presence of fluid. Two intraoperative factors following internal limiting membrane (ILM) peeling were associated with the formation of persistent subfoveal fluid: EZ-RPE height and SRHR width (P < 0.01). These were both negatively correlated with amount of postoperative subfoveal fluid (P = 0.028 and 0.04, respectively). CONCLUSIONS Persistent subfoveal fluid following MH surgery is a common finding that appears to delay visual recovery but not effect final visual outcome. The incidence of persistent subfoveal fluid appears to be related to intraoperative alterations after ILM peeling in the outer retinal architecture (e.g., increased EZ-RPE height and SRHR width). This finding suggests a novel mechanism for facilitating MH closure through ILM peeling (e.g., altering photoreceptor/RPE adherence and increasing retinal mobility that allows for complete hole closure).

Assessment of Retinal Alterations after Intravitreal Ocriplasmin with Spectral Domain-Optical Coherence Tomography

Ocriplasmin (Jetrea, Thrombogenics, Leuvin, Belgium) was recently FDA-approved for the treatment of symptomatic vitreomacular traction (VMT). The MIVI-TRUST phase 3 randomized control trials revealed that intravitreal ocriplasmin had superior efficacy for VMT resolution compared to placebo vehicle injection.1 Qualitative identification of outer retinal changes following ocriplasmin injection that were not previously recognized in the MIVI-TRUST trials have recently been described.2, 3, 4 In those reports, the outer segment ellipsoid zone (EZ), also referred to as inner segment/outer segment (IS/OS) junction, appeared to be most impacted. Another retinal alteration that has been described following ocriplasmin injection is increased subretinal fluid (SRF).2 The purpose of this study was to quantitatively evaluate retinal structural changes with spectral domain OCT (SD-OCT) following ocriplasmin therapy. This was an IRB-approved retrospective consecutive case series and adhered to the tenets of the Declaration of Helsinki. Inclusion criteria included eyes that received intravitreal ocriplasmin and SD-OCT imaging at baseline and at least 1 week following injection. Exclusion criteria included poor quality SD-OCT and concurrent macular disease that could affect visual acuity (VA) and/or retinal architecture. All eyes received intravitreal ocriplasmin (125 µg). The SD-OCT examinations were performed with a Cirrus HD-OCT (Cirrus V.6.1 software, Carl Zeiss Meditec, Dublin, CA) at baseline and at post-injection time points. Inner, middle and outer retinal thicknesses 1.2 mm nasal, temporal, superior, and inferior to the fovea were calculated as previously described.5 Additionally, the distance between the EZ to retinal pigmentary epithelium (EZ-RPE height) was quantified. All measurements were performed in a masked fashion. For SRF volumetric analysis, a custom OCT software analysis program was utilized to manually segment the SRF volume. To compare two groups, Mann-Whitney U tests were used with nonparametric distribution data. Multivariate analysis was used to investigate the relationships between retinal architectural alterations and VA. Spearman’s rank correlation was also performed, as appropriate. A p-value of < 0.05 was considered to be significant. Nineteen eyes of 19 patients were identified that met the inclusion/exclusion criteria for this study. Mean age was 69.6 years (59–85) with 5 men (26%) and 14 women (74%). Twelve (63%) eyes were phakic and 7 (37%) eyes were pseudophakic. The mean visual acuity was 20/40 at baseline, 20/43 at 1 week post-injection, 20/38 at 1 month, and 20/32 at 3 months. Three months after injection, VMT release following ocriplasmin injection was observed in 9 of 19 (47%) eyes. On SD-OCT analysis, 10 of 19 (53 %) eyes exhibited transient EZ loss [Figures 1 and 2 (available at http://aaojournal.org)]. Inner and middle retinal thicknesses were unchanged following ocriplasmin therapy. Mean outer retinal thickness significantly decreased at 1 week (p = 0.00029), but gradually recovered at 1 month (p = 0.09) and 3 months (p = 0.91) following injection. The mean EZ-RPE height at baseline was significantly reduced at 1 week, at 1 month and at 3 months (p = 0.0001, < 0.0001, 0.00099, respectively) following injection (Figure 1). Figure 1 (A) Features identified on OCT 1 week following intravitreal ocriplasmin, including vitreomacular traction release, ellipsoid zone (EZ) loss and subretinal fluid (SRF) accumulation. (B) Bar graph comparing value of EZ-retinal pigment epithelium (RPE) ... Retinal thickness assessments based on VMT release and SRF accumulation were also performed. One week after injection, EZ-RPE height was reduced in eyes with VMT release (14.9 ± 9.1µm compared to baseline) and without VMT release (8.9 ± 13.2 µm). One week following injection, the EZ-RPE height was reduced in eyes with increased SRF (21.9 ± 4.5 µm) but not in eyes without increased SRF (−0.52 ± 2.0 µm) and this was significantly different (p = 0.00024), Figure 1 and Table 1 (available at http://aaojournal.org). The amount of decreased EZ-RPE height was strongly correlated to accumulation of SRF accumulation (p = 0.00021, correlation coefficient = 0.88), Figure 1. As with any retrospective analysis, there are limitations to this study. The follow-up period is relatively short and the sample size small. Due to the retrospective nature, standardized follow-up could not be achieved. This study was also not controlled and did not have a comparison group, such as surgery, placebo injection, or pneumatic vitreolysis. Functional analysis within this study did not include potential important diagnostic testing, including ERG and microperimetry. Recent case reports following ocriplasmin suggests similar acute panretinal dysfunction in rare cases. Outer retinal changes on SD-OCT and significant reduction in ERG amplitudes were present.3, 4 One report suggests that these changes may reflect degradation of laminin resulting in panretinal dysfunction secondary to ocriplasmin.4 In our study, 10 of 19 eyes showed decreased length between the EZ and RPE (EZ-RPE height) one week after ocriplasmin injection. All of these cases also exhibited increased SRF. This EZ-RPE height loss gradually recovered with time. Three months following injection, outer retinal thickness recovered to baseline. The origin of the increased SRF remains unclear. Potential hypotheses include alterations from vitreoretinal traction, transient breakdown of the outer blood-retinal barrier, inherent RPE dysfunction, and accumulation of photoreceptor outer segments. All cases that showed reduction in EZ-RPE height also showed an increase in volume of the SRF compared to baseline. There was a strong correlation in the change in EZ-RPE height and increase in SRF. This may support that the SRF origin is related to the degradation of photoreceptor outer segments. Although the hyporeflective nature of the SRF seen in our cases does not correspond with the typical OCT reflectivity of outer segments, in the presence of potential enzymatic changes it is unclear what characteristics outer segments would have on OCT. In addition, the the loss of standard directional orientation of the outer segments would change the OCT appearance. It is important to recognize that although the EZ band appears to rapidly reappear on the OCT qualitatively within a few weeks, it takes significantly longer for the baseline EZ-RPE height to be restored to preinjection levels. This may reflect the slow reaccumulation of the outer segments. Based on our review of the literature, we believe this represents the first quantitative assessment of the retinal alterations associated with ocriplasmin therapy. Our study suggests that the outer retinal changes and subretinal fluid accumulation appear to be common findings following intravitreal ocriplasmin injection and potentially interrelated. Retinal alterations appear to nearly normalize by 3 months, but the long-term implications of these findings need further prospective research.

Vitrectomy with or without internal limiting membrane peeling for each stage of myopic traction maculopathy.

Purpose: To evaluate the effect of vitrectomy on the best-corrected visual acuity (BCVA) and postoperative complications in highly myopic eyes with myopic traction maculopathy. Methods: The medical records of 71 eyes of 64 patients with myopic traction maculopathy and high myopia (⩽−8.0 diopters and axial length, ≥26.0 mm) were reviewed. Twenty-six eyes had only macular retinoschisis, 30 eyes had foveal detachment, and 15 eyes had macular hole. The BCVA and complications were studied in eyes that underwent vitrectomy with or without internal limiting membrane (ILM) peeling. Results: The postoperative BCVA at the final visit significantly improved in the macular retinoschisis and the foveal detachment groups (P = 0.003 and P = 0.010, respectively) but not in the macular hole group (P = 0.069). The BCVA in the macular retinoschisis group and the foveal detachment group with ILM peeling significantly improved at the final visit (P = 0.003 and P = 0.010, respectively). The BCVA at the final visit significantly correlated with age (P = 0.026) and ILM peeling (P = 0.034). A recurrence of tractional macular detachment developed more frequently in eyes without ILM peeling (P = 0.018). Conclusion: These results indicate that vitrectomy with ILM peeling can lead to improvement in vision in patients with macular retinoschisis or foveal detachment with visual impairments.

Volumetric ellipsoid zone mapping for enhanced visualisation of outer retinal integrity with optical coherence tomography

Objective assessment of retinal layer integrity with optical coherence tomography (OCT) is currently limited. The ellipsoid zone (EZ) has been identified as an important feature on OCT that has critical prognostic value in macular disorders. In this report, we describe a novel assessment tool for EZ integrity that provides visual and quantitative assessment across an OCT data set. Using this algorithm, we describe the findings in multiple clinical examples, including normal controls, age-related macular degeneration, drug effects (eg, ocriplasmin, hydroxychloroquine) and effects of surgical manipulation (eg, following membrane peeling using intraoperative OCT). EZ mapping provides both en face visualisation of EZ integrity and EZ-retinal pigment epithelium height. Additionally, volumetric, area and linear measurements are feasible using this assessment tool.

ELLIPSOID ZONE MAPPING AND OUTER RETINAL CHARACTERIZATION AFTER INTRAVITREAL OCRIPLASMIN.

Purpose: To assess outer retinal architectural alterations after intravitreal ocriplasmin with a novel automated ellipsoid zone (EZ) mapping algorithm. Methods: A single-center, retrospective, consecutive case series of image analysis was performed. Quantitative assessment of EZ status imaged with spectral-domain optical coherence tomography was performed before and after single intravitreal injection of 0.125 mg of ocriplasmin (Jetrea, Thrombogenics). A novel EZ mapping algorithm was used to assess the EZ retinal pigment epithelium (RPE) central area, EZ–RPE macular volume, and en face EZ integrity based on the percentage of sampling areas with 20 &mgr;m or greater EZ–RPE thickness. Longitudinal assessment of these changes with custom optical coherence tomography reading software was completed. Clinical characteristics and outcomes were compared with these retinal changes. Results: Nineteen eyes were included in this study. The retinal volume between EZ and RPE was significantly reduced at 1 week after ocriplasmin (P = 0.0036). Seven of 19 patients (36.8%) complained of color abnormalities or brightness reduction after injection. All of these seven patients had increased subretinal fluid after ocriplasmin and EZ attenuation. The EZ–RPE volume was reduced at 1 week (P = 0.0036), 1 month (P = 0.015) after ocriplasmin, and restored by 3 months. The area with EZ–RPE thickness below 20 &mgr;m was increased at 1 week (P = 0.046) after ocriplasmin and recovered with time. Conclusion: Mapping of EZ is feasible to assess EZ–RPE volume and overall EZ integrity with en face thickness mapping. Alterations in EZ occur in a significant proportion of eyes after ocriplasmin therapy. The EZ–RPE volume and the EZ–RPE central foveal area typically recover to baseline by 3 months. This effect appears to be panretinal and associated with subjective symptoms.

Prevalence and characteristics of hyporeflective preretinal tissue in vitreomacular interface disorders

Aims To assess prevalence and characteristics of hyporeflective preretinal tissue on spectral domain optical coherence tomography (SDOCT) in eyes with vitreomacular interface disorders. Methods 4037 eyes (3195 patients) with diagnosis of lamellar macular hole (LMH), full-thickness macular hole (FTMH), epiretinal membrane (ERM) and vitreomacular traction were included. Quantitative analysis was performed including volume and area of the epiretinal proliferation, as well as the brightness of the hyporeflective band. Clinical characteristics were also collected and analysed. Results A hyporeflective preretinal tissue layer was identified in 204 of 4037 eyes (5.1%); 162 eyes in LMH (79.4%), 23 eyes in FTMH (11.3%) and 19 eyes in ERM (9.3%). In LMH, the visual acuity was significantly different between the cases with and without epiretinal proliferation at the initial visit and the final visit, (p=0.012, 0.046, respectively). The maximum thickness, area, volume of hyporeflective preretinal tissue became significantly larger during the observation period (p<0.001). Brightness of the preretinal tissue (109.3±21.1 arbitrary unit) was close to the retinal ganglion cell layer (112.0±19.5) and the retinal outer plexiform layer (117.7±19.5). Conclusions Hyporeflective preretinal tissue was found with significant frequency in eyes with LMH, FTMH and ERM, with a particularly high incidence in LMH. The increased presence of this tissue in cases of LMH may signify a particular subtype of LMH. More research is needed to better understand the implications of the presence of this tissue for visual and surgical outcomes.

Correlation between foveal interdigitation zone band defect and visual acuity after surgery for macular pseudohole.

Purpose: To determine the correlation between the integrity of the foveal microstructures and the best-corrected visual acuity (BCVA) after pars plana vitrectomy for a macular pseudohole. Methods: Thirty-one eyes of 31 patients with a macular pseudohole underwent vitrectomy with internal limiting membrane removal. The foveal area was examined by spectral domain optical coherence tomography preoperatively and postoperatively. The correlations between the BCVA and the lengths of the photoreceptor interdigitation zone (IZ), the ellipsoid zone, and the external limiting membrane band defects, and central foveal thickness were determined. Results: The BCVA improved significantly and the length of the IZ band defect decreased significantly after the surgery. Simple linear regression analyses showed that the BCVA was significantly correlated with the length of the IZ band defect preoperatively and also at 1 to 12 months postoperatively (P < 0.001 for all). The BCVA was not significantly correlated with the length of the ellipsoid zone, external limiting membrane band defect, and the central foveal thickness. Conclusion: The significant correlation between the length of the foveal IZ band defect and the BCVA preoperatively and postoperatively indicates that the foveal IZ band is related to the visual recovery in patients with macular pseudohole.

Inverted Internal Limiting Membrane Flap Technique For Treatment Of Macular Hole Retinal Detachment In Highly Myopic Eyes

Purpose: To compare the efficacy of vitrectomy with inverted internal limiting membrane (ILM) flap to complete removal of the ILM for the treatment of macular hole (MH) retinal detachment in highly myopic eyes. Methods: Pars plana vitrectomy with inverted ILM flap technique (16 eyes; inverted group) or with the complete removal of the ILM (16 eyes; removed group) was performed in patients with high myopia with MH retinal detachment. The rate of retinal reattachment and MH closure, the best-corrected visual acuities, and the integrity of the foveal microstructures in the optical coherence tomographic images were compared. Results: Thirteen eyes (81%) in the inverted group and 15 eyes (93%) in the removed group had retinal reattachment after the initial surgery (P = 0.30). The MH was closed significantly more often in the inverted group (75%) than in the removed group (25%; P = 0.006). The postoperative best-corrected visual acuity was significantly better in the inverted group (P = 0.04). The number of eyes with outer nuclear layer, external limiting membrane, and ellipsoid zone lines at the closed MH was not significantly different in the two groups. Conclusion: The inverted ILM flap technique with the presence of bridging tissue over the MH is effective in closing the MH and improving the postoperative best-corrected visual acuity in eyes with MH retinal detachment by bridging tissue over the MH.

DURATION OF PRONE POSITIONING AFTER MACULAR HOLE SURGERY DETERMINED BY SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY

Purpose: To compare the closure rate of macular hole closure and duration of the prone positioning after macular hole (MH) surgery with two protocols for halting the prone positioning. Methods: The authors studied 129 eyes of 125 consecutive patients with MH who had undergone vitrectomy. In 60 eyes of 59 patients, the prone positioning was halted after detecting an MH closure in the swept-source optical coherence tomographic images (SS group). In 69 eyes of 66 patients, the prone position was halted by the surgeons decision (conventional group). The MH closure rate and duration of the prone positioning were compared. Results: Clear images of the MH were recorded in the SS group on postoperative Day 1 in 58 eyes (97%). In the SS group, MH closure was detected on postoperative Day 1 in 47 eyes (78%) and Day 2 in 4 eyes (7%). The MH was closed in 58 eyes (97%) in the SS group and 69 eyes (100%) in the conventional group (P = 0.21). None of the eyes had a reopening of the MH. The duration of prone positioning in the SS group was 1.8 ± 2.5 days, which was significantly shorter than that in the conventional group at 8.4 ± 4.2 days (P < 0.0001). Conclusion: The SS-OCT protocol can significantly decrease the duration of the prone positioning without a reopening of the MH.