Inflammation after Voretigene Neparvovec Administration in Patients with RPE65-Related Retinal Dystrophy.

PURPOSE: To report on the prevalence of intraocular inflammation after subretinal voretigene neparvovec (VN) administration. DESIGN: Retrospective review of medical files. PARTICIPANTS: All patients receiving VN in Denmark. METHODS: Twelve patients received VN gene therapy as standard of care for biallelic RPE65-related retinal disease. Bilateral treatment was performed in 11 patients and unilateral treatment in 1 patient. Patients were followed clinically before and after VN administration using functional measurements (visual acuity, full-field scotopic threshold test, visual fields) and structural evaluations (fundus imaging [color and autofluorescence], OCT, slit-lamp). MAIN OUTCOME MEASURES: Signs of intraocular inflammation, including vitritis and outer retinal infiltrates. RESULTS: Vitritis was observed in 9 of 23 eyes receiving VN. The median time to resolution of vitritis from the time of treatment was 89 days. Four eyes also presented with outer retinal infiltrates at the time of vitritis. Inflammation subsided on immunosuppressant therapy. The presence of inflammation did not adversely affect visual outcome after VN therapy. In 1 eye, outer retinal infiltrates were demonstrated to precede later development of atrophy. CONCLUSIONS: Patients undergoing subretinal gene therapy need to be closely monitored for signs of inflammation. Although we did not observe a detrimental effect on visual function in eyes with inflammation, it seems wise to treat it appropriately because it may lead to atrophy of the retinal pigment epithelium and outer retina. Also, it seems advisable to reduce the inflammatory load, such as using a surgical technique that minimizes residual viral vectors in the vitreous body.

Effects of age on muscle power, postural control and functional capacity after short-term immobilization and retraining.

OBJECTIVES: This study investigated the effect of lower limb immobilization and retraining on postural control and muscle power in healthy old and young men. METHODS: Twenty men, nine old (OM:67.3±4.4 years) and eleven young (YM:24.4±1.6 years) underwent 2 weeks of unilateral whole-leg casting, followed by 4 weeks of retraining. Measures included center of pressure (CoP) sway length and area during single- and double-leg stance, maximal leg extensor muscle power, habitual and maximal 10-m gait speed, sit-to-stand performance, and 2-min step test. RESULTS: After immobilization, leg extension muscle power decreased by 15% in OM (from 2.68±0.60 to 2.29±0.63 W/kg, p<0.05) and 17% in YM (4.37±0.76 to 3.63±0.69 W/kg, p<0.05). Double-leg CoP sway area increased by 45% in OM (218±82 to 317±145 mm2; p<0.05), with no change in YM (p=0.43). Physical function did not change after immobilization but sit-to-stand performance (+20%, p<0.05) and 2-min step test (+28%, p<0.05) increased in OM following retraining. In both groups, all parameters returned to baseline levels after retraining. CONCLUSION: Two weeks of lower limb immobilization led to decreases in maximal muscle power in both young and old, whereas postural control was impaired selectively in old men. All parameters were restored in both groups after 4 weeks of resistance-based retraining.

Vitrectomy with internal limiting membrane peeling versus no peeling for idiopathic full-thickness macular hole.

OBJECTIVE: To determine whether internal limiting membrane (ILM) peeling improves anatomic and functional outcomes of full-thickness macular hole (FTMH) surgery when compared with the no-peeling technique. DESIGN: Systematic review and individual participant data (IPD) meta-analysis undertaken under the auspices of the Cochrane Eyes and Vision Group. Only randomized controlled trials (RCTs) were included. PARTICIPANTS AND CONTROLS: Patients with idiopathic stage 2, 3, and 4 FTMH undergoing vitrectomy with or without ILM peeling. INTERVENTION: Macular hole surgery, including vitrectomy and gas endotamponade with or without ILM peeling. MAIN OUTCOME MEASURES: Primary outcome was best-corrected distance visual acuity (BCdVA) at 6 months postoperatively. Secondary outcomes were BCdVA at 3 and 12 months; best-corrected near visual acuity (BCnVA) at 3, 6, and 12 months; primary (after a single surgery) and final (after >1 surgery) macular hole closure; need for additional surgical interventions; intraoperative and postoperative complications; patient-reported outcomes (PROs) (EuroQol-5D and Vision Function Questionnaire-25 scores at 6 months); and cost-effectiveness. RESULTS: Four RCTs were identified and included in the review. All RCTs were included in the meta-analysis; IPD were obtained from 3 of the 4 RCTs. No evidence of a difference in BCdVA at 6 months was detected (mean difference, -0.04; 95% confidence interval [CI], -0.12 to 0.03; P=0.27); however, there was evidence of a difference in BCdVA at 3 months favoring ILM peeling (mean difference, -0.09; 95% CI, -0.17 to-0.02; P=0.02). There was evidence of an effect favoring ILM peeling with regard to primary (odds ratio [OR], 9.27; 95% CI, 4.98-17.24; P<0.00001) and final macular hole closure (OR, 3.99; 95% CI, 1.63-9.75; P=0.02) and less requirement for additional surgery (OR, 0.11; 95% CI, 0.05-0.23; P<0.00001), with no evidence of a difference between groups with regard to intraoperative or postoperative complications or PROs. The ILM peeling was found to be highly cost-effective. CONCLUSIONS: Available evidence supports ILM peeling as the treatment of choice for patients with idiopathic stage 2, 3, and 4 FTMH.

A nationwide study on the incidence of rhegmatogenous retinal detachment in Denmark, with emphasis on the risk of the fellow eye.

PURPOSE: To estimate the risk of developing rhegmatogenous retinal detachment (RRD) in the fellow eye in patients with RRD in the first eye and to identify potential risk factors. METHODS: We used the Danish National Patient Registry to identify all surgeries performed for RRD in Denmark in the period from January 2000 to July 2011. RESULTS: In 11,451 cases of RRD in the study period, 8,553 cases in 8,081 patients were identified as primary RRD with an annual incidence of 13.7 per 100,000 citizens. There was a significant increase in the number of cases with RRD during the study period that was mainly explained by an increase of cataract surgeries. Four hundred and seventy-one of 7,941 patients with primary RRD on one eye and no other previous eye disease developed an additional RRD in the fellow eye with an overall incidence of 1% per year. Cox analysis revealed male gender, surgery on the lens, and young age as significant risk factors (P < 0.0001). CONCLUSION: Patients with RRD on the first eye have a 100 times greater risk of developing RRD on the second eye, and the risk increases with male gender and surgery on the lens but decreases with age.

Location and Extent of Paravascular Nerve Fiber Layer Clefts in Eyes with Epiretinal Membranes.

Purpose: The clinical use of en face optical coherence tomography (OCT) has revealed nerve fiber layer clefts in the retinal nerve fibers in eyes with macula-centered epiretinal membranes (ERMs). The purpose of this study is to describe the location and the extent of retinal nerve fiber layer (RNFL) clefts in eyes with symptomatic ERMs. Methods: We conducted a retrospective review of 17 individual eyes in 17 patients with symptomatic ERMs and a control group of 10 healthy eyes from 10 subjects who had been examined for unrelated causes. The examinations performed included best-corrected visual acuity, rebound tonometry, fundus photography, structural OCT and angiographic OCT (OCTA) made in the form of 12 × 12 mm angiographic volume scans. Results: Hyporeflective RNFL clefts, seen in 14 out of 17 eyes with ERMs, were sharply demarcated in the en face presentation of slabs extending from the internal limiting membrane through the RNFL or including only the latter. The clefts were capillary-free on OCTA scans and formed depressions of the retinal surface. Most of the clefts were adjacent to and followed the course of the retinal trunk vessels, but clefts were also seen along smaller macular vessels and beyond the retinal vascular arcades. Conclusions: Paravascular RNFL clefts can be observed beyond the vascular arcades and adjacent to small vessels on OCTA block scan data. This suggests that the direction and magnitude of tractional displacement of the inner retina in eyes with epimacular membranes can extend beyond the vascular arcades and add to an improved analysis of abnormal fundus findings.

Preoperative Positioning and Progression of Fovea-on Retinal Detachments.

PURPOSE: To study the relationship between positioning and rhegmatogenous retinal detachment (RRD) progression before surgery in patients with a fovea-on RRD. DESIGN: Prospective, single-cohort study. SUBJECTS: Patients with fovea-on RRD admitted to hospital for bedrest before surgical treatment were recruited. METHODS: Primary outcome was the shortest distance from the foveal center to the retinal detachment border on OCT. Secondary outcomes were measured with a head-mounted positioning sensor and included measures of head movement (linear acceleration and angular velocity) as well as measures of positioning regimen compliance. MAIN OUTCOME MEASURES: Distance from the fovea to the retinal detachment border. RESULTS: Overall, 50 patients with fovea-on positioned before RRD repair. One patient (1/50, 2%) progressed from fovea-on to fovea-off. Of the positioning measures, angular velocity demonstrated the strongest correlation with RRD border movement, whereas measures of positioning compliance showed nonsignificant correlation. After defining 3 movement groups: stable, intermediate, and mobile RRDs, we found that a doubling of head movement (angular velocity) correlated with a median RRD border progression of -6 µm/h, -75 µm/h, and -219 µm/h in the 3 groups, respectively. CONCLUSIONS: Rhegmatogenous retinal detachment border movement is correlated to angular velocity of the head, whereas compliance with our current positioning regimen does not have a significant impact on RRD border movement. Not all RRDs progress rapidly toward the fovea, but those that do seem to be highly influenced by head movement. For limiting RRD progression, a reduced movement positioning regimen may be superior to our current gravity-based approach. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The role of phacoemulsification surgery in the incidence rate of rhegmatogenous retinal detachment.

PURPOSE: To investigate changes in the incidence rate of primary rhegmatogenous retinal detachment (RRD) surgery over time and to determine to what extent these changes can be attributed to pseudophakia. METHODS: This nationwide cohort study was based on national patient registries. The study population comprised individuals at risk of RRD aged 40 years and above from 2006 to 2021 in Denmark. The primary outcome was RRD incidence, and the exposure was phacoemulsification surgery. A chart review was conducted to validate and examine the lens status of the outcome. RESULTS: The crude and age-adjusted incidence rate of RRD in the Danish population increased significantly during the study period. The largest increase in RRD was seen in phakic RRD (phRRD) (65%), whereas pseudophakic RRD (pRRD) accounted for 35% of the total increase. A chart review revealed that 17% of phRRDs were misclassified as pseudophakic, resulting in pRRD accounting for a total of 45% of the increase in RRD. The prevalence of pseudophakia in Denmark grew significantly for all age groups and for both sexes (p = 10-6) from 2006 to 2021, but the 1-year incidence of pRRD in the pseudophakic population was constant throughout the entire period. CONCLUSION: The incidence rate of RRD is continuing to increase in Denmark. The increase in phRRD remains undetermined, and while the risk of pRRD seemed to be constant during the study period, 45% of the overall increase in RRD could be attributed to the rise of a growing pseudophakic population.

Wound Healing in a Porcine Model of Retinal Holes.

Purpose: To investigate retinal wound healing, we created a new porcine model of retinal hole and identified the cells involved in hole closure. Methods: Sixteen landrace pigs underwent vitrectomy, and a subretinal bleb was created before cutting a retinal hole using a 23G vitrector. No tamponade was used. Before surgery and one, two, and four weeks after surgery, the eyes were examined by optical coherence tomography and color fundus photos. At the end of follow-up, the eyes were enucleated for histology. Tissue sections of 5 µm were prepared for hematoxylin-eosin staining and immunohistochemical analysis with antibodies to retinal glial and epithelial cells. Results: Retinal holes below 1380 µm in diameter closed spontaneously within four weeks, whereas larger holes remained open. Hole closure was mediated by central movement of the edges of the hole and in most cases the formation of a gliotic plug. Fluorescence microscopy revealed that the plug consisted of cells positive for glial fibrillary acidic protein, indicating the presence of macroglial cell types. Specifically, the plug was positive for S100 calcium-binding protein B, mainly representing astrocytes, while it was negative for anti-glutamine syntethase, representing Müller glia. These findings suggest that astrocytes are the predominating cell type in the plug. Minimal glial reaction was seen in the retinal holes that did not close. Conclusions: We present a new porcine model for investigating large retinal holes. The retinal holes closed by approximation of hole edges, and the remnant retinal defect was closed with an astroglial plug.

Association Between Vegetation Size and Outcome in the Partial Oral Antibiotic Endocarditis Treatment Trial.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.

Vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with no peeling for idiopathic full-thickness macular hole (FTMH).

BACKGROUND: Several observational studies have suggested the potential benefit of internal limiting membrane (ILM) peeling to treat idiopathic full-thickness macular hole (FTMH). However, no strong evidence is available on the potential benefit(s) of this surgical manoeuvre and uncertainty remains among vitreoretinal surgeons about the indication for peeling the ILM, whether to use it in all cases or in long-standing and/or larger holes.  OBJECTIVES: To determine whether ILM peeling improves anatomical and functional outcomes of macular hole surgery compared with the no-peeling technique and to investigate the impact of different parameters such as presenting vision, stage/size of the hole and duration of symptoms in the success of the surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane Eyes and Vision Group Trials Register (The Cochrane Library 2013, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to February 2013), EMBASE (January 1980 to February 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to February 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 February 2013.We searched reference lists of the studies included in the review for information about other studies on ILM peeling in macular hole surgery. We searched Proceedings for the following conferences up to February 2013: American Academy of Ophthalmology (AAO), Annual Meeting of the American Society of Retina Specialists (ASRS), Annual Meeting of the Retina Society, Congress of the Asia-Pacific Academy of Ophthalmology (APAO), European Association for Vision and Eye Research (EVER) Annual Congress, European Vitreoretinal Society (EVRS) Annual Meeting, Association for Research in Vision and Ophthalmology (ARVO) Meeting, International Vitreoretinal Meeting, and World Ophthalmology Congress. SELECTION CRITERIA: Only randomised controlled trials (RCTs) comparing ILM peeling with the no-peeling counterpart were included. DATA COLLECTION AND ANALYSIS: Two review authors (KSC and NL) independently assessed the titles and abstracts of all RCTs identified by electronic and manual searches.We obtained Individual patient data (IPD) from three of the four identified eligible trials. The fourth identified RCT had only been published in abstract form and no IPD were available; we included data from this published abstract for one outcome (macular hole closure).The primary outcome was distance visual acuity at six months. Secondary outcomes included distance and near  visual acuity at three and 12 months postoperatively, near visual acuity at six months postoperatively, primary (after a single surgery) and final (following more than one surgery) macular hole closure, need for additional surgical interventions, vision-related quality of life and intraoperative and postoperative complications.We performed meta-analysis using standard techniques (the Mantel-Haenszel odds ratio (OR) for binary outcomes, mean difference (MD) for continuous outcomes) using a fixed-effect model. For two outcomes we also used the IPD to perform adjusted analyses using regression methods. MAIN RESULTS: We identified and included four RCTs; these were conducted in Denmark, France, Hong Kong and the United Kingdom/Republic of Ireland and randomised 47, 80, 49 and 141 participants respectively.There was no evidence of a difference in the primary outcome (distance visual acuity at six months), nor in distance visual acuity at 12 months between randomised groups. However, there was evidence of improved best corrected distance visual acuity in the ILM peeling group at three months (WMD -0.09, 95% CI -0.17 to -0.02). We found no evidence for a difference in near vision between groups at any of the time points investigated.Overall, more participants in the ILM peeling group than in the no-peeling group had primary macular hole closure (OR 9.27, 95% CI 4.98 to 17.24); this held true when results were stratified by the stage of the macular hole. There was also evidence that those in the ILM peeling group were more likely to have final macular hole closure (OR 3.99, 95% CI 1.63 to 9.75). Fewer participants required further surgery in the ILM peeling group than in the no-peeling group (OR 0.11, 95% CI: 0.05 to 0.23).Rates of intraoperative and postoperative complications were similar in both groups.Based on the results of one study, there was no evidence that total VFQ-25 or EQ-5D scores differed between the groups at six months.  Based on this same study, ILM peeling is highly likely to be cost-effective. AUTHORS' CONCLUSIONS: Although we found no evidence of a benefit of ILM peeling in terms of the primary outcome (visual acuity at six months), ILM peeling appears to be superior to its no-peeling counterpart as it offers more favourable cost effectiveness by increasing the likelihood of primary anatomical closure and subsequently decreasing the likelihood of further surgery, with no differences in unwanted side-effects compared with no peeling. 

[Gene therapy for hereditary eye diseases].

Inherited retinal disorders (IRD) are a common cause of severe visual impairment among children and young adults in Denmark. Gene therapy with voretigene neparvovec for a specific, and in Denmark common, cause of IRD (RPE65-related retinal dystrophy) was implemented as standard clinical practice in 2020 as the first of its kind. Twelve Danish patients have been treated with very positive outcomes. Genetically based therapies for other genetic causes of IRD are underway in clinical trials and are expected to change the outlooks for patients who would otherwise become blind early in life.

Quantifying surgical skill in macular surgery.

PURPOSE: To evaluate the relationship between patient outcome and surgical experience by developing an objective quality measure of macular hole surgery based on forceps damage to the inner retina. METHODS: We retrospectively examined 3 macular hole case series >1 year after pars plana vitrectomy, internal limiting membrane peeling and gas tamponade. The patients were operated by (1) a novice surgeon (<20 cases), (2) an intermediate (150+ cases) and (3) an experienced surgeon (2000+ cases). Primary outcome was inner retinal volume defect as segmented from optical coherence tomography (GCL++: thickness from internal limiting membrane to inner plexiform layer). Secondary outcome was retinal function measured by confocal microperimetry using a custom scanning protocol. RESULTS: Thirty-two patients were examined: 11, 10 and 11 patients in the novice, intermediate and experienced surgeon group, respectively. Median GCL++ volume defect was 23.68 × 106 µm3 (IQR: 22.77 × 106 -44.81 × 106 µm3 ), 8.42 × 106 µm3 (IQR: 4.86 × 106 -10.03 × 106 µm3 ) and 3.55 × 106 µm3 (IQR: 1.44 × 103 -7.94 × 106 µm3 ) in the novice, intermediate and experienced surgeon group, respectively (p = 0.0004). The novice surgeon volume defect differed significantly from the intermediate and experienced surgeon (p = 0.016 and p = 0.0002, respectively). A subset of 12 patients underwent microperimetry measurements demonstrating correlation between inner retinal volume defect and reduced retinal sensitivity (p = 0.02). CONCLUSIONS: Forceps induced inner retinal damage commonly occurs during initiation of internal limiting membrane peeling in macular hole surgery. Damage to the structure and function of the inner retina seems to correlate to surgical experience.

Measuring aniseikonia tolerance range for stereoacuity - a tool for the refractive surgeon.

OBJECTIVE: No method exists to measure aniseikonia tolerance in stereoacuity. The brain can compensate for 2%-3% aniseikonia (i.e. 2-3 dioptres of anisometropia) without impairing stereoacuity; however, a substantial proportion of anisometropic patients experience problems caused by disruptions of sensory fusion due to surgically induced aniseikonia. We hypothesized that individual differences in tolerance to aniseikonia exist and sought to develop a method to measure aniseikonia tolerance. METHODS: A total of 21 eye-healthy phakic individuals older than 50 years of age and 11 patients awaiting clear lens extraction were included. Patients were tested with best corrected near and distance visual acuity, cover/uncover test, eye dominance test, stereoacuity threshold (TNO test), slit lamp examination and ocular coherence tomography. The stereoacuity threshold was determined with aniseikonia induced by different size lenses ranging from 1% to 9% magnification of both eyes in increments of 1%. The aniseikonia tolerance range (ATR) was defined as the percentage aniseikonia in which the stereoacuity threshold was maintained. RESULTS: We examined 32 patients with a median age of 65 (95% CI: 62-66 years), CDVA better than 6/7.5 (0.1 logMAR), and median near visual acuity better than 6/6 (0.0 logMAR). The median stereoacuity threshold was 60 arcsec (maximum 30, minimum 120). We observed large inter-individual differences in ATR: 6/31 (19%) participants had an ATR of ≤1%, 1/31 (3%) had an ATR of 1-5%, 7/31 (22%) had an ATR of 5-10%, and 17/31 (54%) had an ATR of >10%. CONCLUSION: We present a reliable method for measuring the amount of aniseikonia that a person can tolerate without impairing stereopsis. We report large inter-individual differences in tolerance of aniseikonia.

The tolerance of anisometropia.

PURPOSE: This study examines aniseikonia, Aniseikonia tolerance range (ATR), anisometropia and patient-reported outcomes (PRO) in an anisometropic population compared with a non-anisometropic population. The relationship between anisometropia and aniseikonia is determined, and the correlations between aniseikonia, anisometropia and ATR versus PRO are described. METHODS: One hundred and twenty-three patients with IOL-induced anisometropia ≥1 dioptre (D) (the anisometropic group) and 17 patients who had IOL-induced anisometropia <1 D (the control group) were included. Best corrected visual acuity, aniseikonia, ATR and stereoacuity were examined, and two questionnaires were completed: convergence insufficiency symptom survey (CISS) and Visual Function Questionnaire (VFQ-39). RESULTS: One hundred and thirteen patients had anisometropia >1 and <3 D, and 10 patients had anisometropia >3 D. There was no difference in PRO between the control group and the anisometropic group (Mann-Whitney, p-values VFQ: 0.96, CISS: 0.06). There was no correlation between anisometropia and PRO (Spearman's rank correlation test p-values: VFQ: 0.54, CISS: 0.57). Patients with low ATR were more sensitive towards anisometropia and had lower PRO than patients with high ATR (Mann-Whitney, p-values: VFQ: 0.0008, CISS: 0.11). A large tolerance of aniseikonia was observed. CONCLUSION: No correlation between PRO and anisometropia or aniseikonia was found. Patients with low ATR are at risk of visual complaints if they are exposed to IOL-induced anisometropia. ATR might be a future screening tool in cataract patients.

Monocular and binocular end-points after epiretinal membrane surgery and their correlation to patient-reported outcomes.

PURPOSE: This study evaluates current available endpoints for epiretinal membrane (ERM) surgery and examine their correlation to patient reported outcomes (PRO). METHODS: Retrospective study including 38 eyes of 38 patients who underwent cataract extraction and subsequent vitrectomy for idiopathic ERM. The fellow eye was phakic with good visual acuity. The registered outcomes were monocular and binocular visual acuity, stereoacuity, M-chart metamorphopsia score, aniseikonia and aniseikonia tolerance range (ATR). Two questionnaires were completed: the convergence insufficiency symptom survey and Visual Function Questionnaire (VFQ-39). RESULTS: Median total aniseikonia was 11% (range 0-35). There was a statistically significant correlation between the mean total M-chart score of the study eye and VFQ-Near (Spearman rho: VFQ-Near: -0.54, p < 0.01). There was no correlation between the best corrected visual acuity (BCVA) of the project eye, binocular BCVA, stereoacuity, ATR or mean total aniseikonia and PRO (Spearman p-values > 0.05). There was no correlation between mean total aniseikonia and mean total M-chart score (Spearman rho: 0.21 p = 0.26). There was a large variation between the mean total M-chart scores and questionnaire results. CONCLUSION: The mean total M-chart score is currently the best end-points to predict PRO of ERM surgery; however, it is possible to have high M-chart values and have no visual complaints.

Prognostic significance of delayed structural recovery after macular hole surgery.

PURPOSE: To assess the prognostic significance for visual function of persistent subfoveal fluid and persistent photoreceptor layer discontinuity in eyes in which hole closure had been obtained 3 months after macular hole surgery. DESIGN: Ancillary study of subjects enrolled in a randomized clinical trial. PARTICIPANTS: Participants were recruited from a randomized clinical trial evaluating internal limiting membrane (ILM) peeling in macular hole surgery. The study included 74 eyes in which a contiguous retinal surface or a full attachment with a flat neuroretinal rim had been reestablished after macular hole surgery. METHODS: Contrast-enhanced optical coherence tomography was used to detect closure defects involving substrata of the retina with particular emphasis on the photoreceptor layer. Outcomes were compared with best-corrected visual acuity (BCVA) 12 months after surgery. MAIN OUTCOME MEASURES: Postoperative foveal configuration and foveal photoreceptor layer discontinuity diameter 3 months after macular hole surgery. RESULTS: Persistent subfoveal fluid 3 months after macular hole surgery, which was found in 36.5% of eyes, was not associated with a significantly different BCVA after 12 months compared with eyes with a fully attached fovea at 3 months (70.9 letters vs. 72.0 letters; P = 0.59). Receiver operating characteristics curve analysis identified persistent photoreceptor layer discontinuity of a diameter of more than 1477 microm after 3 months to be associated with poorer BCVA after 12 months (P<0.001), yet an overall reduction in discontinuity diameter from 3 to 12 months (P<0.001) was not correlated with a concurrent improvement in BCVA (r = -0.040; P = 0.81). Persistence of fluid and diameter of discontinuity at 3 months were not related to whether ILM peeling was used; however, secondary macular hole surgery had a significant influence on diameter of photoreceptor layer discontinuity at 3 months. CONCLUSIONS: Structural recovery in the form of photoreceptor layer discontinuity with a diameter of more than approximately 1500 microm 3 months after macular hole surgery was associated with poorer visual acuity after 12 months than less extensive discontinuity. Subfoveal fluid persisting after 3 months had disappeared after 12 months in all but 5 of 74 eyes and had no effect on final visual outcome.

Epiretinal membrane surgery: an analysis of 2-step sequential- or combined phacovitrectomy surgery on refraction and macular anatomy in a prospective trial.

PURPOSE: To assess the impact of combined phacoemulsification-vitrectomy and sequential surgery for idiopathic epiretinal membrane (ERM) on refractive error (RE) and macular morphology. METHODS: In this prospective clinical trial, we allocated phakic eyes with ERM to (1) cataract surgery and subsequent pars plana vitrectomy (PPV) (CAT group), (2) PPV and subsequent cataract surgery (VIT group) or (3) phaco-vitrectomy (COMBI group). Examinations were at baseline, one month after each surgery, and at 3 months and 12 months of follow-up. Primary outcome was the RE (the difference between predicted and achieved spherical equivalent); secondary outcomes were best-corrected visual acuity (BCVA), and incidence of cystoid macular oedema (CME) defined as >10% increment of central subfield macular thickness (CSMT). RESULTS: Sixty-two eyes were enrolled. The mean RE showed a small myopic shift of -0.36D in all groups 1 month after surgery, decreasing after 12 months to -0.17D. The absolute value of the RE (ARE) ranged 0.49-0.68D after 12 months. In the immediate postoperative period, there was a higher incidence of CME in the CAT group. There was no significant difference in final RE, ARE, BCVA and CSMT between the groups. Four cases (17%) in the CAT group had resolved visual complaints and improved BCVA after cataract surgery resulting in no need for PPV within the follow-up period. CONCLUSION: Surgery for idiopathic ERM in phakic eyes with either phaco-vitrectomy or sequential surgery are equal approaches with respect to functional- (RE, BCVA) and anatomical outcomes (CME, CSMT). However, if starting with cataract surgery, 17% of the cases may not need subsequent PPV.

Laser pointer maculopathy - on the rise?

PURPOSE: To report symptoms and ocular pathology in 13 patients exposed to light from laser pointers. METHODS: We conducted a multi-centre consecutive case series from eight ophthalmology departments. RESULTS: Eleven boys aged 9-15 years and two girls aged 7 (sister of one of the aforementioned boys) and 12 years, respectively, were included. Laser wavelengths were 572 nm (green), 450 nm (blue), and red laser of unknown wavelength. Output powers were between 5 and 5000 mW. Evaluation included slit lamp examination, colour fundus photography (CFP), and optical coherence tomography (OCT). All subjects complained of unilateral vision loss. Initial visual acuities in exposed eyes ranged from 0.05 to 1.0 Snellen equivalent or better. Nine subjects showed pathology on CFP and OCT abnormalities. One subject had a macular hole, which closed after vitrectomy. Long-term visual acuity ranged from 0.3 to 1.0 Snellen equivalent or better. CONCLUSION: High-powered laser pointers have become readily available on the internet, and they have the potential to induce lasting visual loss. More than half of the published laser pointer maculopathy cases since the first incidence in 1999 have been published in 2014-2017. We suspect that incidence of exposure and subsequent visual loss is rising, and we encourage national legislators to regulate this market.

Enhancing the signal-to-noise ratio in ophthalmic optical coherence tomography by image registration--method and clinical examples.

Optical coherence tomography (OCT) has already proven an important clinical tool for imaging and diagnosing retinal diseases. Concerning the standard commercial ophthalmic OCT systems, speckle noise is a limiting factor with respect to resolving relevant retinal features. We demonstrate successful suppression of speckle noise from mutually aligning a series of in vivo OCT recordings obtained from the same retinal target using the Stratus system from Humphrey-Zeiss. Our registration technique is able to account for the axial movements experienced during recording as well as small transverse movements of the scan line from one scan to the next. The algorithm is based on a regularized shortest path formulation for a directed graph on a map formed by interimage (B-scan) correlations. The resulting image enhancement typically increases the contrast-to-noise ratio (CNR) with a factor of three or more and facilitates segmentation and quantitative characterization of pathologies. The method is currently successfully being applied by medical doctors in a number of specific retinal case studies.