CHOROIDEREMIA: Retinal Degeneration With an Unmet Need Purpose: Choroideremia is an incurable, X-linked, recessive retinal dystrophy caused by loss of function mutations in the CHM gene. It is estimated to affect approximately 1 in 50,000 male patients. It is characterized by progressive degeneration of the retinal pigment epithelium, choroid, and photoreceptors, resulting in visual impairment and blindness. There is an unmet need in choroideremia, because currently, there are no approved treatments available for patients with the disease. Methods: We review the patient journey, societal impact, and emerging treatments for patients with choroideremia. Results: Its relative rarity and similarities with other retinal diseases in early years mean that diagnosis of choroideremia can often be delayed. Furthermore, its impact on affected individuals, and wider society, is also likely underestimated. AAV2-mediated gene therapy is an investigational treatment that aims to replace the faulty CHM gene. Early-phase studies reported potentially important visual acuity gains and maintenance of vision in some patients, and a large Phase 3 program is now underway. Conclusion: Choroideremia is a disease with a significant unmet need. Interventions that can treat progression of the disease and improve visual and functional outcomes have the potential to reduce health care costs and enhance patient quality of life. |
LONG-TERM VISUAL OUTCOMES AND CLINICAL FEATURES AFTER ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION–RELATED ENDOPHTHALMITIS Purpose: To determine long-term visual outcomes in patients who developed endophthalmitis after intravitreal anti–vascular endothelial growth factor injections and to correlate visual outcomes with clinical features. Methods: This is a retrospective, multicenter, consecutive case series of patients diagnosed with anti–vascular endothelial growth factor injection–related endophthalmitis who were treated at Mid Atlantic Retina, the Retina Service of Wills Eye Hospital, Philadelphia, PA, and the University of Southern California Roski Eye Institute, Los Angeles, CA. Patients were included if they had at least 1 year of follow-up. Primary outcome was to evaluate long-term visual outcomes up to 5 years of follow-up. The secondary outcome was to determine clinical features (e.g., culture results) that may predict long-term visual acuity outcomes. Results: A total of 56 cases of endophthalmitis from 168,247 anti–vascular endothelial growth factor injections were identified (0.033%, 1/3,004 injections), from which 51 eyes met inclusion criteria. Mean follow-up period was 3.3 years (median 4 years; range 1–5 years). A total of 24 patients (47%) reached a maximum final follow-up of 5 years. Mean Snellen visual acuity at the causative injection visit was 20/102 and decreased to counting fingers at diagnosis (P < 0.001). At 6-month follow-up, mean visual acuity improved to 20/644 (P < 0.001) and remained stable up to 5 years (20/480, P = 0.003) follow-up compared with diagnosis. At the final follow-up, 20 eyes had visual acuity that returned to within one line of baseline visual acuity (visual recovery group), whereas 31 patients' visual acuity was at least one line worse than initial visual acuity (visual deterioration group). The cultures for the visual recovery group were more likely to grow coagulase-negative Staphylococcus, whereas the visual deterioration group primarily grew Streptococcus species, Staphylococcus aureus, and Enterococcus faecalis (P = 0.002, comparing organisms isolated in the visual recovery and deterioration group). Conclusion: Visual outcomes after anti–vascular endothelial growth factor injection–related endophthalmitis seem to reach peak improvement by 6 months and remain stable up to a median of 4-year follow-up. Patients who develop culture-negative endophthalmitis or endophthalmitis secondary to coagulase-negative Staphylococcus are more likely to regain baseline visual acuity compared with cases secondary to Streptococcus species. |
TWELVE-MONTH OUTCOMES OF INTRAVITREAL AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Fixed Versus As-needed Dosing Purpose: To compare the clinical outcomes of aflibercept used with a fixed schedule with a pro-re-nata (PRN) retreatment regimen in patients affected by neovascular age-related macular degeneration. Methods: This is a prospective multicenter, noninferiority, propensity score–matched study evaluating the 12-month outcomes of aflibercept given either according to labeling or following a PRN regimen. Patients included in the latter group received one initial injection, followed by monthly visits and as-needed retreatment. Results: One-to-one matching resulted in fixed and PRN arms containing 92 eyes each. Visual acuity improved from baseline to 12 months in both the study groups. At Month 4, the fixed regimen was equivalent to the PRN regimen (mean difference: 1.75 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: −1.42 to +4.92). The pro-re-nata regimen failed to show noninferiority compared with the fixed regimen at both Month 8 (mean difference: 3.43 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: +0.25 to +6.22) and Month 12 (mean difference: 4.83 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: +1.37 to +8.29). All patients in the fixed group received seven injections. Patients included in the PRN arm received a mean of 5.5 ± 1.6 treatments. Conclusions: Aflibercept given with a fixed treatment regimen produces better visual acuity outcomes than an individualized regimen. |
STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF LAMELLAR MACULAR HOLES Purpose: Lamellar macular holes (LMHs) can been subdivided into tractional and degenerative subtypes. This cross-sectional cohort study compared structural and functional characteristics in these subtypes hypothesizing that tractional LMH has a higher prevalence of vitreopapillary adhesion and tangential traction (macular pucker), whereas degenerative LMH has more ellipsoid zone disruption and worse vision, measured three different ways. Methods: Tractional LMH (n = 22) and degenerative LMH (n = 15) were distinguished by optical coherence tomography criteria. Separate spectral domain optical coherence tomography scanning of the macula and optic disk was performed. Visual acuity, contrast sensitivity function (Weber Index, %W), and the degree of visual distortions (3-dimensional threshold Amsler grid; % volume lost [%VL]) were quantified. Results: Vitreopapillary adhesion was present in 14/22 (64%) tractional, but in only 3/15 (20%) degenerative LMH (P = 0.006). Macular pucker was present in 19/22 (86%) tractional, but in only 8/15 (53%) degenerative LMH (P = 0.011). Ellipsoid zone disruption was present in 13/15 (87%) degenerative, but in only 2/22 (9%) tractional LMH (P = 0.0001). Visual acuity was better in tractional than degenerative LMH (P = 0.006), as was contrast sensitivity function (tractional = 3.44 ± 1.07 %W, degenerative = 4.66 ± 1.73 %W; P = 0.015). Visual distortions were less in tractional (0.33 ± 0.61 %VL) than in degenerative (0.85 ± 0.68 %VL) LMH (P = 0.014). Conclusion: Structure and visual function differ significantly in subtypes of LMH. Tractional LMH has 3-fold higher prevalence of vitreopapillary adhesion and 2-fold higher prevalence of macular pucker. Degenerative LMH has 9-fold more ellipsoid zone disruption, worse visual acuity and contrast sensitivity function, and 3-fold more distortions. Thus, outer retinal integrity seems more closely correlated with vision than anterior structural abnormalities in LMH. |
PARS PLANA VITRECTOMY FOR THE TREATMENT OF TRACTIONAL AND DEGENERATIVE LAMELLAR MACULAR HOLES: Functional and Anatomical Results Purpose: Functional and anatomical outcomes of vitrectomy with membrane peeling were compared in tractional lamellar macular holes (LMH)/macular pseudoholes (MPH) versus degenerative LMH. Methods: This multicenter retrospective study enrolled patients with a minimum follow-up of 6 months. The association of spectral domain optical coherence tomography parameters with preoperative and postoperative best-corrected visual acuity was analyzed. Results: Seventy-seven (74.8%) tractional LMH/MPH and 26 (25.2%) degenerative LMH were included. Preoperative best-corrected visual acuity was better in tractional LMH/MPH (0.39 ± 0.2 logarithm of the minimal angle of resolution, 20/50 Snellen equivalent) than degenerative LMH (0.56 ± 0.2 logarithm of the minimal angle of resolution, 20/66 Snellen equivalent; P < 0.001). Premacular membranes were found in all tractional LMH/MPH, whereas LMH-associated epiretinal proliferation (LHEP) was present in all degenerative LMH. Primary anatomical success was achieved in 97/103 eyes (94.2%), with foveal restoration occurring earlier in degenerative LMH (1.6 ± 2.3 vs. 3.3 ± 3.6 months; P = 0.025). Best-corrected visual acuity improved in both tractional LMH/MPH and degenerative LMH (P < 0.001 and P = 0.012, respectively) but was better in tractional LMH/MPH (P = 0.001). Conclusion: The presence of premacular membranes and absence of LMH-associated epiretinal proliferation in all tractional LMH/MPH further distinguishes this from degenerative LMH. Best-corrected visual acuity improved in both subgroups but more so in tractional LMH/MPH. Complete anatomical restoration of foveal microanatomy was rare in degenerative LMH, reflecting significant morphological and pathophysiological differences between the two lesions. |
SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY TO DETERMINE THE RECOVERY OF RETINAL LAYERS AFTER INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR MACULAR HOLE: Correlation With Visual Acuity Improvement Purpose: To analyze the recovery of retinal lines using swept-source optical coherence tomography after inverted internal limiting membrane flap technique to treat full-thickness macular hole, and the relationship between best-corrected visual acuity and retinal line repair. Methods: Thirty-eight eyes were evaluated for recovery of the external limiting membrane, photoreceptor inner segment/outer segment junction line, and cone outer segment tips (COST) line. Correlation between the recovery of retinal lines and best-corrected visual acuity improvement was analyzed 6 months after surgery. Results: The closure rate of full-thickness macular hole was 97%. The best recovery rates were associated with external limiting membrane line recovery (25 eyes, 65.8%), followed by inner segment/outer segment line recovery (22 eyes, 57.9%), and less frequently, COST line recovery (9 eyes, 23.7%); moreover, recovery of the COST line was apparent only in eyes with recovered external limiting membrane and inner segment/outer segment lines. Mean postoperative visual acuity in the COST line recovery group (COST+) was 20/42 (0.48, 0.33 logarithm of the minimum angle of resolution), compared with 20/95 (0.21, 0.68 logarithm of the minimum angle of resolution) without COST line recovery (COST−). Final visual acuity was significantly better in the COST+ group compared with the COST− group (P = 0.002). Conclusion: Cone outer segment tips line recovery is correlated with best-corrected visual acuity improvement for eyes treated with inverted internal limiting membrane flap technique for full-thickness macular hole. |
LATE-ONSET OCULAR HYPERTENSION AFTER VITRECTOMY: A Multicenter Study of 6,048 Eyes Purpose: To determine the incidence and risk factors for late-onset ocular hypertension (LOH) after vitrectomy. Methods: From the electronic medical records of consecutive patients who underwent primary vitrectomy, from January 2010 to December 2015, at 5 tertiary vitreoretinal centers in Italy, patient demographics, systemic, ophthalmic, operative, and postoperative data were drawn. Main outcome measure was the presence of LOH, defined as intraocular pressure >21 mmHg detected more than 2 months after vitrectomy on at least 2 consecutive visits. Results: Among 6,048 patients, LOH was found in 294 (4.9%) vitrectomized eyes and in 87 (1.4%) fellow eyes, (chi square; P < 0.001). Multivariable logistic regression showed that significant risk factors for developing LOH included intraoperative triamcinolone use (odds ratio [OR], 7.62; P < 0.001), longer axial length (OR, 1.55; P = 3.023), preoperative higher intraocular pressure (OR, 1.81; P = 0.003), and postvitrectomy pseudophakic/aphakic status (OR, 2.04; P < 0.001). Decision-tree analysis showed that the stronger predictor of LOH was intraoperative triamcinolone use (P < 0.001). Secondary predictors were a preoperative intraocular pressure more than 15 mmHg (P < 0.001) in eyes that use triamcinolone, and postvitrectomy pseudophakic/aphakic status (P = 0.007) in eyes that did not use triamcinolone. Conclusion: Late-onset ocular hypertension occurred in 4.9% of vitrectomized eyes. The main risk factors were intraoperative use of triamcinolone and postvitrectomy pseudophakic/aphakic status. |
EPIRETINAL MEMBRANE REMOVAL WITH FOVEAL-SPARING INTERNAL LIMITING MEMBRANE PEELING: A Pilot Study Purpose: To compare the retinal sensitivity after complete internal limiting membrane (ILM) peeling with that after foveal-sparing ILM peeling during vitrectomy for Type I epiretinal membrane. Methods: This was a prospective, randomized, comparative study. Thirty-eight eyes were randomized to undergo complete peeling of the ILM (CP group) or peeling with foveal sparing (FS group). The main outcome measures were foveal and perifoveal retinal sensitivity, visual acuity, and central retinal thickness. Results: Foveal retinal sensitivity showed a significant improvement in the FS group (2.82 ± 0.85 dB, P = 0.037) versus a slight drop in the CP group (−0.66 ± 0.48 dB, P = 1). Perifoveal retinal sensitivity slightly improved in both groups (0.47 ± 0.37 dB, P = 1 in the CP group and 0.79 ± 0.42 dB, P = 0.77 in the FS group), showing a similar trend without significant differences. Significant improvements were observed in both visual acuity and central retinal thickness in both groups. However, three cases in the FS group showed epiretinal membrane recurrence and required revision surgery with complete ILM removal. Conclusion: Internal limiting membrane peeling may reduce retinal sensitivity and significantly increase the incidence of microscotomas. However, the higher epiretinal membrane recurrence rate after the foveal-sparing technique limits the effectiveness of this procedure. Further studies must be conducted to determine if it is safe to leave a portion of the ILM in front of the fovea. |
VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING AND AIR TAMPONADE FOR MYOPIC FOVEOSCHISIS Purpose: To evaluate the functional and anatomical outcomes of 23-gauge or 25-gauge pars plana vitrectomy with internal limiting membrane peeling and air tamponade for the treatment of myopic foveoschisis. Methods: Retrospective, noncomparative, interventional case series. The records of 29 patients (32 eyes), with myopic foveoschisis who were treated by 23-gauge or 25-gauge 3-port pars plana vitrectomy with internal limiting membrane peeling and air tamponade, were reviewed. At each visit, a complete ophthalmic examination, intraocular pressure, best-corrected visual acuity, and central foveal thickness measured using optical coherence tomography were assessed. Results: Twenty-five eyes of 23 patients (M:F = 4:19) matched the inclusion criteria, whereas 7 eyes of 6 patients were excluded. The mean logarithm of the minimum angle of resolution best-corrected visual acuity (Snellen equivalent) was 0.62 (20/80) (SE: 0.061), and the mean preoperative central foveal thickness was 619.5 µm (SE: 16.38) at baseline. Visual acuity significantly improved of 5 Early Treatment Diabetic Retinopathy Study letters (45 letters) at the 1-month follow-up (P < 0.001), 2 lines (50 Early Treatment Diabetic Retinopathy Study letters) at the 6-month follow-up (P < 0.001), and it reached 55 Early Treatment Diabetic Retinopathy Study letters at the 1-year follow-up visit (P < 0.001). Central foveal thickness decreased to 292.4 µm (SE: 15.93), to 227.3 µm (SE: 14.05), and to 208.8 µm (SE: 12.86), respectively, at the 1-, 6-, and 12-month follow-ups (for each P < 0.001). There were no differences in best-corrected visual acuity or central foveal thickness changes between the foveal detachment group and the nonfoveal detachment group (P > 0.05). Conclusion: Small-gauge vitrectomy with internal limiting membrane peeling and air tamponade results in favorable anatomical and functional outcomes for patients affected by myopic macular foveoschisis. |
PATIENTS WITH EPIRETINAL MEMBRANES DISPLAY RETROGRADE MACULOPATHY AFTER SURGICAL PEELING OF THE INTERNAL LIMITING MEMBRANE Purpose: Intraretinal cystoid spaces are commonly found after surgical peeling of epiretinal membranes. In this study, we explored whether these cysts were associated with ganglion cell loss and thus might be a manifestation of retrograde maculopathy. The latter is a nonvascular edema with a characteristic morphology that is often found in the inner nuclear layer (INL) of patients with optic neuropathy. Methods: In this retrospective case series, we identified consecutive patients who underwent surgical epiretinal membrane peeling. We determined the frequency of microcystic macular edema (MME), defined by vertical cystoid spaces in the INL, and we measured the thickness of individual macular layers before and after surgery. Results: Epiretinal membrane peeling resulted in an improvement of visual acuity and a reduction of retinal thickness by about 15%. In total, 35% of patients with MME before surgery showed no sign of MME postoperatively, whereas edema persisted after surgery in 65% of patients. Interestingly, 29% of the patients without MME before surgery developed MME after surgery. Overall, we found MME in 35% of patients before peeling and in 42% after peeling. After surgery, the mean ganglion cell layer thickness was reduced compared with healthy control eyes. Ganglion cell layer thickness correlated inversely with thickness of the INL. Compared with patients without MME, individuals with MME had a thinner ganglion cell layer and a thicker INL in the affected eye. Conclusion: Our findings indicate that peeling of epiretinal membranes and internal limiting membranes is associated with atrophy of ganglion cells and thickening of the INL. The latter is associated with the presence of MME. Altogether, we assume that surgical treatment of epiretinal membranes induces a variant of a retrograde maculopathy. |
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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Δευτέρα 28 Οκτωβρίου 2019
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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00302841026182,
00306932607174,
alsfakia@gmail.com,
Anapafseos 5 Agios Nikolaos 72100 Crete Greece,
Medicine by Alexandros G. Sfakianakis,
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