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.

[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.

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.

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.

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.

Corneal endothelial cell loss and corneal biomechanical characteristics after two-step sequential or combined phaco-vitrectomy surgery for idiopathic epiretinal membrane.

PURPOSE: To assess the impact of sequential and combined surgery [cataract surgery and 23-gauge pars plana vitrectomy (PPV) with peeling] on corneal endothelium cell density (CED) and corneal biomechanical characteristics. METHODS: Phakic eyes with epiretinal membrane (ERM) were prospectively allocated to (i) cataract surgery and subsequent PPV (CAT group), (ii) PPV and subsequent cataract surgery (VIT group) or (iii) phacovitrectomy (COMBI group). Eyes were examined at baseline, 1 month after each surgery, and at 3 and 12 months follow-up. Corneal endothelium cell density (CED) was assessed with non-contact specular microscopy. Pachymetry [central cornea thickness (CCT)], keratometry and cornea volume (CV) were measured with Pentacam Scheimpflug camera. Primary outcome was change in CED after 12 months; secondary outcomes were changes in CCT and CV after 12 months. RESULTS: Sixty-two eyes were enrolled and allocated to the three groups. The mean preoperative CED was 2776, 2794 and 2653 cells/mm2, which decreased significantly at 12 months by 15.3, 20.0 and 19.3% in the CAT, VIT and COMBI group. There was no significant difference in percentage cell loss between the groups at final follow-up. The CED decreased significantly after cataract surgery, but was unaffected by PPV. Central cornea thickness (CCT) increased by 10 µm (p = 0.005) and CV by 1.38 mm3 (2.3%, p < 0.001) in the COMBI group. There were no significant differences in CCT or CV between the groups at final follow-up. CONCLUSION: Combined and sequential surgery in ERM leads to a small decrease in CED. Performing cataract surgery before, after or in combination with vitrectomy did not make any significant difference with respect to final CED, CCT or CV.

Value of internal limiting membrane peeling in surgery for idiopathic macular hole and the correlation between function and retinal morphology.

Idiopathic macular hole is characterized by a full thickness anatomic defect in the foveal retina leading to loss of central vision, metamorphopsia and a central scotoma. Classic macular hole surgery consists of vitrectomy, posterior vitreous cortex separation and intraocular gas tamponade, but during the past decade focus has especially been on internal limiting membrane (ILM) peeling as adjuvant therapy for increasing closure rates. With increasing use of ILM peeling and indocyanine green (ICG) staining, which is used for specific visualization of the ILM, concerns about the safety of the procedure have arisen. At present, it is not known whether ICG-assisted ILM peeling potentially reduces the functional outcome after macular hole surgery. The purpose of the present PhD thesis was to examine whether ICG-assisted ILM peeling offers surgical and functional benefit in macular hole surgery. We conducted a randomized clinical trial including 78 pseudophakic patients with idiopathic macular hole stages 2 and 3. Patients were randomly assigned to macular hole surgery consisting of (i) vitrectomy alone without instrumental retinal surface contact (non-peeling), (ii) vitrectomy plus 0.05% isotonic ICG-assisted ILM peeling or (iii) vitrectomy plus 0.15% trypan blue (TB)-assisted ILM peeling. Morphologic and functional outcomes were assessed 3, 6 and 12 months after surgery. The results show that surgery with ILM peeling, for both stages 2 and 3 macular holes, is associated with a significantly higher closure rate than surgery without ILM peeling (95% versus 45%). The overall functional results confirm that surgery for macular hole generally leads to favourable visual results, with two-thirds of eyes regaining reading vision (>or=20/40). Macular hole surgery can be considered a safe procedure with a low incidence of sight-threatening adverse events; the retinal detachment rate was 2.2%. Visual outcomes in eyes with primary hole closure were not significantly different between the intervention groups; however, for the stage 2 subgroup with primary macular hole closure, there was a trend towards a better mean visual acuity in the non-peeling group (78.2 letters) compared to the ICG-peeling group (70.9 letters), p = 0.06. Performing repeated macular hole surgery was associated with a significant reduction in functional outcome indicating that primary focus should be on closing the macular hole in one procedure. Morphological studies of closed macular holes with contrast-enhanced optical coherence tomography (OCT) found thinning and discontinuity of the central photoreceptor layer matrix that were highly specific for predicting the likelihood of an eye having regained reading vision 12 months after macular hole surgery. Additionally, healing after macular hole surgery appeared to begin with the contraction of the inner aspect of the retina, forming a roof over a subfoveal fluid-filled cavity, and to end with a gradual restoration of the anatomy in the outer layers of the retina at the junction of the photoreceptor inner and outer segments. We found the more intact this structure was on contrast-enhanced OCT 3 months after macular hole surgery, the better the visual acuity after 12 months, whereas late rather than early resolution of subfoveal fluid had no impact on final visual outcome. The use ILM peeling and intraoperative dyes did not have any functionally important effects on postoperative macular structure. Based on the above findings, we conclude that ILM peeling should be performed in all cases of full thickness macular hole surgery. The use of 0.05% intraoperative isotonic ICG with short exposure time appears to be a safe alternative in stage 3 macular hole surgery, whereas a slight reduction in functional potential not can be excluded when performing 0.05% isotonic ICG-assisted ILM peeling in stage 2 macular hole surgery.