Large Idiopathic Macular Hole Surgery: Remodelling of Outer Retinal Layers after Traditional Internal Limiting Membrane Peeling or Inverted Flap Technique.

OBJECTIVE: To investigate the influence of the inverted flap technique compared with traditional internal limiting membrane (ILM) peeling in the postoperative remodelling of outer retinal layers of idiopathic macular holes (MHs) >450 µm. METHODS: We analyzed medical records and imaging studies of all patients with an idiopathic MH >450 µm who underwent vitrectomy at the Sacco University Hospital, Milan, and the Sacro Cuore Don Calabria Hospital, Verona, Italy, between January 2008 and December 2017. Out of 41 eyes evaluated, 17 were treated with traditional ILM peeling and 24 with the inverted ILM flap technique. All patients underwent follow-up examinations every 3 months and all of them completed a final visit 12 months after surgery. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters were evaluated at each visit. The main outcome measures were the postoperative recovery rate of the external limiting membrane (ELM) and ellipsoid zone (EZ), and postoperative BCVA. Correlations between OCT measurements and visual outcome were analyzed. RESULTS: The ELM recovery rate in the ILM peeling group (15/17 eyes, 88%) was higher than in the ILM flap group (14/24 eyes, 58%) (p = 0.079). The EZ recovery rate was similar in the 2 groups, 7/17 eyes (41%) in the ILM peeling and 8/24 eyes (33%) in the ILM flap group (p = 0.744). Eyes without a persistent hyper-reflective "plug" at the edges of the MH showed a significantly higher EZ recovery rate (11/18, 61%) compared with eyes showing a persistent plug (4/23, 17%) (p = 0.008). The mean BCVA improved significantly in both groups: from 0.93 logMAR (20/170) to 0.26 logMAR (20/36) in the ILM peeling and from 0.98 logMAR (20/190) to 0.37 logMAR (20/46) in the ILM flap group. The final BCVA tended to be better in the ILM peeling group (p = 0.085). CONCLUSIONS: Given the limited information about the influence of ILM flap versus traditional ILM peeling in the postoperative remodelling of large idiopathic MHs, our data provides some new insights into the healing process of MHs >450 µm. This should be considered as part of the decision process about whether to perform an ILM flap in these patients.

Frequency of NFKBIA deletions is low in glioblastomas and skewed in glioblastoma neurospheres.

The NF-kB family of transcription factors is up-regulated in inflammation and different cancers. Recent data described heterozygous deletions of the NF-kB Inhibitor alpha gene (NFKBIA) in about 20% of glioblastomas (GBM): deletions were mutually exclusive with epidermal growth factor receptor (EGFR) amplification, a frequent event in GBM. We assessed the status of NFKBIA and EGFR in 69 primary GBMs and in corresponding neurospheres (NS). NFKBIA deletion was investigated by the copy number variation assay (CNV); EGFR amplification by CNV ratio with HGF; expression of EGFR and EGFRvIII by quantitative PCR or ReverseTranscriptase PCR. Heterozygous deletions of NFKBIA were present in 3 of 69 primary GBMs and, surprisingly, in 30 of 69 NS. EGFR amplification was detected in 36 GBMs: in corresponding NS, amplification was lost in 13 cases and reduced in 23 (10 vs 47 folds in NS vs primary tumors; p < 0.001). The CNV assay was validated investigating HPRT1 on chromosome X in females and males. Results of array-CGH performed on 3 primary GBMs and 1 NS line were compatible with the CNV assay. NS cells with NFKBIA deletion had increased nuclear activity of p65 (RelA) and increased expression of the NF-kB target IL-6. In absence of EGF in the medium, EGFR amplification was more conserved and NFKBIA deletion less frequent point to a low frequency of NFKBIA deletions in GBM and suggest that EGF in the culture medium of NS may affect frequency not only of EGFR amplifications but also of NFKBIA deletions.

Lamellar macular defects: are degenerative lamellar macular holes truly degenerative?

Purpose: To investigate morpho-functional changes after surgical treatment for ERM foveoschisis or lamellar macular hole (LMH), and to evaluate whether the two entities are associated with different healing processes and long-term outcomes. Design: Retrospective interventional case series. Methods: A total of 56 eyes, treated for lamellar macular defects and followed up for 24 months, were enrolled. The eyes were divided into two groups: 34 with ERM foveoschisis and 22 with LMH. Changes in the following features were evaluated and compared between the two groups: best-corrected visual acuity (BCVA), external limiting membrane (ELM) and ellipsoid zone (EZ) defects, central foveal thickness (CFT), and autofluorescence (FAF) diameter and area. Results: After surgery, progressive BCVA improvement was observed with no significant difference between the two groups (p-value: 0.06). An increased number of eyes with intact outer-retinal layers was found both in the ERM foveoschisis and LMH groups. FAF diameter and area decreased significantly throughout the FU with no significant difference between the two groups (p-value: 0.2). Conclusion: In the present study, significant functional and microstructural improvements were observed after surgery for both ERM foveoschisis and LMH, demonstrating considerable repair potential in both types of lamellar defects. These findings question the true "degenerative" nature of LMH.

Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation.

PURPOSE: The purpose of this study was to evaluate and compare microperimetry and fundus autofluorescence (FAF) after subthreshold micropulse diode laser versus modified Early Treatment Diabetic Retinopathy Study photocoagulation for clinically significant diabetic macular edema. METHODS: A prospective randomized clinical trial including 62 eyes (50 patients) with untreated, center-involving, clinically significant diabetic macular edema was performed. All patients underwent best-corrected visual acuity determination (logarithm of the minimum angle of resolution), slit-lamp biomicroscopy, FAF, optical coherence tomography, microperimetry (macular sensitivity), and fluorescein angiography before and after treatment. Best-corrected visual acuity, optical coherence tomography, microperimetry, and FAF were repeated at 1-, 3-, 6-, 9-, and 12-month follow-up examinations. Fluorescein angiography was performed at baseline and at 6 and 12 months. RESULTS: Before treatment, demographic and macular parameters were not different between the two treatment groups. At 12 months, best-corrected visual acuity remained stable in both groups (P = 0.41 and P = 0.82), mean central retinal thickness decreased in both groups (P = 0.0002 and P < 0.0001), and mean central 4 degrees and 12 degrees retinal sensitivity increased in the micropulse diode laser group (P = 0.02 and P = 0.0075) and decreased in the Early Treatment Diabetic Retinopathy Study group (P = 0.2 and P = 0.0026). There was no significant difference in either best-corrected visual acuity or central retinal thickness between the 2 treatment groups (P = 0.48 and P = 0.29), whereas there was a significant difference in 4 degrees and 12 degrees retinal sensitivity (P = 0.04 and P < 0.0001). Fundus autofluorescence never changed in the micropulse diode laser group even after retreatment. In the Early Treatment Diabetic Retinopathy Study group, FAF increased up to 9 months and decreased in 6 eyes (20%) at 12 months. DISCUSSION: Micropulse diode laser seems to be as effective as modified Early Treatment Diabetic Retinopathy Study laser photocoagulation in the treatment of clinically significant diabetic macular edema. Micropulse diode laser treatment does not determine any change on FAF showing (at least) nonclinically visible damage of the retinal pigment epithelium. Microperimetry data encourage the use of a new, less aggressive laser therapeutic approach in the treatment of clinically significant diabetic macular edema.

Retinal fixation impairment in diabetic macular edema.

PURPOSE: To evaluate the characteristics of retinal fixation in patients with diabetic macular edema using microperimetry. METHODS: One hundred seventy nine eyes (98 patients) with untreated diabetic macular edema underwent best corrected visual acuity determination (Early Treatment Diabetic Retinopathy Study charts), digital color stereoscopic fundus photos, fluorescein angiography and Optical Coherence Tomography assessment of macula. Fixation and retinal thresholds were determined with an automatic microperimeter. RESULTS: Best corrected visual acuity (approximate Snellen equivalent) was: 20/25 or better in 90 (52%) eyes, 20/50 to 20/32 in 39 (22.5%) eyes, 20/200 to 20/62.5 in 35 (20.2%) eyes and inferior to 20/200 in 9 (5.2%) eyes. Fixation was central in 128 (71.51%), poor central in 26 (14.53%) and predominantly eccentric in 25 (13.97%) eyes; stable in 133 (74.3%), relatively unstable in 42 (23.46%) and unstable in 4 (2.23%) eyes. Both fixation location and stability were not significantly influenced by edema characteristics (diffuse, focal, cystoid, spongelike, with or without subfoveal neuroretinal detachment), (P > 0.05), whereas they were significantly influenced by the presence of subfoveal hard exudates, (P = 0.004 and P = 0.0046, respectively). Site and stability of fixation were significantly associated, (P < 0.0001). Retinal pseudofovea would have been covered by laser photocoagulation in 24 (47%) eyes with poorly central and predominantly eccentric fixation and in 29 (63%) eyes with relatively unstable and unstable fixation. CONCLUSION: Microperimetry shows that fixation location and stability in patients with diabetic macular edema are independent of edema characteristics, except when subfoveal hard exudates are present. Location of pseudofovea may influence treatment strategy.

Scanning laser ophthalmoscopy in the retromode in diabetic macular oedema.

PURPOSE: To determine the validity of scanning laser ophthalmoscopy in the retromode (RM-SLO) versus other imaging modalities in the diagnosis of diabetic macular oedema (DME). METHODS: Two hundred and sixty-three eyes were examined. Inclusion criteria were any stage of untreated or treated diabetic retinopathy and four imaging modalities of the macula carried out on the same day: time domain optical coherence tomography (OCT), fundus autofluorescence (FAF), RM-SLO and fluorescein angiography (FA). Two masked retinal specialists independently graded all images. Agreement between RM-SLO and OCT, FA and FAF in evaluating the presence and patterns of DME was evaluated by kappa statistics, sensitivity, specificity, observed proportional agreement, and proportional agreement in positive and negative cases. RESULTS: The agreement in evaluating the presence/absence of DME between RM-SLO and OCT, FA and FAF was good: κ = 0.73 (confidence interval; CI, 0.64-0.83), κ = 0.71 (CI, 0.61-0.81) and κ = 0.73 (CI, 0.63-0.83), respectively. The agreement in evaluating cystoid pattern of DME was almost perfect between RM-SLO and OCT, RM-SLO and FA, κ > 0.8; and good between RM-SLO and FAF, κ > 0.7. The agreement in evaluating the presence/absence of subfoveal neuroretinal was almost perfect between RM-SLO and OCT (κ = 0.83; 95% CI, 0.70-0.96). Subfoveal neuroretinal detachment did not show any specific pattern on FA or FAF. Sensitivity and specificity of RM-SLO in evaluating DME was 97.7% and 71.9% versus OCT, 97.4% and 68.1% versus FA and 96.1% and 73.3% versus FAF. Retinal thickness of 233 µm represented the cut-off value to define DME by RM-SLO. CONCLUSIONS: The combined use of non-invasive imaging techniques can improve the diagnostic interpretation of different aspects of DME.

PowerRefractor versus Canon R-50 Autorefraction to assess refractive error in children: a community-based study in ecuador.

PURPOSE: To compare the agreement of the PowerRefractor with Canon R-50 autorefraction for measuring refractive error in a community of Ecuadorian children. METHODS: We examined 1564 children aged 5 to 6 years from two ethnically and geographically similar regions of the Ecuadorian highlands. Results of a refraction obtained without cycloplegia with the PowerRefractor and with the Canon R-50 autorefractor (NCAR) were compared with the gold-standard examination, cycloplegic autorefraction (CAR) with the Canon R-50 autorefractor. Power vectors were used to analyze refractive error. Bland-Altman limits of agreement were obtained. RESULTS: Although the mean difference in the spherical equivalent refractive error between the PowerRefractor and CAR was small (-0.03 D +/- 0.05 D), the 95% limits of agreement were wide (+/-2.03 D). On the other hand, NCAR showed a greater bias (0.97 D +/- 0.04 D) and smaller limits of agreement (+/-1.49 D). The limits of agreement of the PowerRefractor were also wider than NCAR for measuring astigmatism. When the mean difference was stratified by the subgroups of refractive error vectors, the PowerRefractor was found to have poorer limits of agreement than NCAR for hyperopic defects. CONCLUSION: The PowerRefractor is accurate, but not as precise for measuring refractive error as compared to the Canon R-50 autorefractor, especially for high hyperopia.