Retinal Vascular Tortuosity in a Patient with Weill-Marchesani Syndrome

Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder with characteristic phenotypic skeletal and ocular manifestations. A 28-year-old myopic female presented with an 8-month history of bilateral blurred vision. On examination, she was noted to be of short stature with brachydactyly. On ocular examination, she was found to be spherophakic with bilateral inferiorly subluxated lenses. Serum and urine homocysteine were normal and a syphilis screen was negative. A diagnosis of Weill-Marchesani syndrome was made. Fundoscopy revealed bilateral tortuous retinal vessels. We report the first illustrated case of retinal vascular tortuosity as an ocular manifestation of Weill-Marchesani syndrome

Direct cost of pars plana vitrectomy for the treatment of macular hole, epiretinal membrane and vitreomacular traction: a bottom-up approach

Purpose The direct cost to the National Health Service (NHS) in England of pars plana vitrectomy (PPV) is unknown since a bottom-up costing exercise has not been undertaken. Healthcare resource group (HRG) costing relies on a top-down approach. We aimed to quantify the direct cost of intermediate complexity PPV. Methods Five NHS vitreoretinal units prospectively recorded all consumables, equipment and staff salaries during PPV undertaken for vitreomacular traction, epiretinal membrane and macular hole. Out-of-surgery costs between admission and discharge were estimated using a representative accounting method. Results The average patient time in theatre for 57 PPVs was 72 min. The average in-surgery cost for staff was £297, consumables £619, and equipment £82 (total £997). The average out-of-surgery costs were £260, including nursing and medical staff, other consumables, eye drops and hospitalisation. The total cost was therefore £1634, including 30 % overheads. This cost estimate was an under-estimate because it did not include out-of-theatre consumables or equipment. The average reimbursed HRG tariff was £1701. Conclusions The cost of undertaking PPV of intermediate complexity is likely to be higher than the reimbursed tariff, except for hospitals with high throughput, where amortisation costs benefit from economies of scale. Although this research was set in England, the methodology may provide a useful template for other countries

Treatment of refractory diabetic macular edema with a fluocinolone acetonide implant in vitrectomized and non-vitrectomized eyes

AIM: To report real-life data on the use of an intravitreal fluocinolone acetonide implant in the treatment of refractory diabetic macular edema (DME) in pars plana vitrectomized (PPV) and non-PPV eyes. METHODS: This was a comparative retrospective observational study of 23 eyes with chronic DME. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were recorded at baseline, 1, 4 and 12mo. Descriptive statistics and non-parametric tests were performed to analyze and compare PPV and non-PPV eyes. RESULTS: Seven PPV and 16 non-PPV eyes were included in the study. Median BCVA in the non-PPV group varied from 0.65 logMAR [Interquartile range (IQR): 0.40] at baseline to 0.42 logMAR (IQR: 0.40) at 12mo. Median CMT varied from 430 µm (IQR: 131.3) at baseline to 317 µm (IQR: 107.5) at 12mo. Median BCVA in the PPV group varied from 0.60 logMAR (IQR: 0.62) at baseline to 0.74 logMAR (IQR: 0.34) at 12mo. Median CMT varied from 483 µm (IQR: 146) at baseline to 397 µm (IQR: 132) at 12mo. Of 0/7 eyes and 1/16 eyes in the PPV and non-PPV eyes respectively had a baseline visual acuity of 6/12 or better (0.3 logMAR). At last follow up, 1/7 and 5/16 eyes in the PPV and non-PPV group respectively achieved a visual acuity of 6/12 or better. CONCLUSION: Visual outcomes are modest following the use of the fluocinolone acetonide implant for chronic DME. The steroid implant is a useful treatment option in the management of refractory DME in vitrectomized and non-vitrectmized eyes

Intraocular Lens Opacification following Intracameral Injection of Recombinant Tissue Plasminogen Activator to Treat Inflammatory Membranes after Cataract Surgery

Purpose. To report 7 cases of intraocular lens (IOL) opacification following treatment of postoperative anterior chamber fibrin with recombinant tissue plasminogen activator (rtPA) after cataract surgery. Methods. Retrospective case series of 7 eyes in 7 patients who developed IOL opacification after receiving rtPA for anterior chamber inflammatory membrane formation resulting from phacoemulsification cataract surgery. Three explanted IOLs were investigated with light microscopy, histochemical analysis, scanning electron microscopy, and X-ray spectrometry. Results. All patients underwent uncomplicated cataract surgery and posterior chamber hydrophilic IOL implantation. Anterior chamber inflammatory membranes developed between 1 and 4 weeks of surgery and were treated with intracameral rtPA. IOL opacification was noted between 4 weeks and 6 years after rtPA treatment with reduced visual acuity, and IOL exchange was carried out in 3 patients. Light microscopy evaluation revealed diffuse fine granular deposits on the anterior surface/subsurface of IOL optic that stained positive for calcium salts. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS) confirmed the presence of calcium and phosphate on the IOL. Conclusions. Intracameral rtPA, though rapidly effective in the treatment of anterior chamber inflammatory membranes following cataract surgery, may be associated with IOL opacification

Apelin Is Required for Non-Neovascular Remodeling in the Retina

Retinal pathologies are frequently accompanied by retinal vascular responses, including the formation of new vessels by angiogenesis (neovascularization). Pathological vascular changes may also include less well characterized traits of vascular remodeling that are non-neovascular, such as vessel pruning and the emergence of dilated and tortuous vessel phenotypes (telangiectasis). The molecular mechanisms underlying neovascular growth versus non-neovascular remodeling are poorly understood. We therefore undertook to identify novel regulators of non-neovascular remodeling in the retina by using the dystrophic Royal College of Surgeons (RCS) rat and the retinal dystrophy 1 (RD1) mouse, both of which display pronounced non-neovascular remodeling. Gene expression profiling of isolated retinal vessels from these mutant rodent models and wild-type controls revealed 60 differentially expressed genes. These included the genes for apelin (Apln) and for its receptor (Aplnr), both of which were strongly up-regulated in the mutants. Crossing RD1 mice into an Apln-null background substantially reduced vascular telangiectasia. In contrast, Apln gene deletion had no effect in two models of neovascular pathology [laser-induced choroidal neovascularization and the very low density lipoprotein receptor (Vldlr)-knockout mouse]. These findings suggest that in these models apelin has minimal effect on sprouting retinal angiogenesis, but contributes significantly to pathogenic non-neovascular remodeling

Radiotherapy for neovascular age-related macular degeneration

BACKGROUND: Radiotherapy has been proposed as a treatment for new vessel growth in people with neovascular age-related macular degeneration (AMD). OBJECTIVES: To examine the effects of radiotherapy on neovascular AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS and three trials registers and checked references of included studies. We last searched the databases on 4 May 2020.  SELECTION CRITERIA: We included all randomised controlled trials in which radiotherapy was compared to another treatment, sham treatment, low dosage irradiation or no treatment in people with choroidal neovascularisation (CNV) secondary to AMD. DATA COLLECTION AND ANALYSIS: We used standard procedures expected by Cochrane. We graded the certainty of the evidence using GRADE. We considered the following outcomes at 12 months: best-corrected visual acuity (BCVA) (loss of 3 or more lines, change in visual acuity), contrast sensitivity, new vessel growth, quality of life and adverse effects at any time point.  MAIN RESULTS: We included 18 studies (n = 2430 people, 2432 eyes) of radiation therapy with dosages ranging from 7.5 to 24 Gy. These studies mainly took place in Europe and North America but two studies were from Japan and one multicentre study included sites in South America. Three of these studies investigated brachytherapy (plaque and epimacular), the rest were studies of external beam radiotherapy (EBM) including one trial of stereotactic radiotherapy. Four studies compared radiotherapy combined with anti-vascular endothelial growth factor (anti-VEGF) with anti-VEGF alone. Eleven studies gave no radiotherapy treatment to the control group; five studies used sham irradiation; and one study used very low-dose irradiation (1 Gy). One study used a mixture of sham irradiation and no treatment. Fifteen studies were judged to be at high risk of bias in one or more domains. Radiotherapy versus no radiotherapy There may be little or no difference in loss of 3 lines of vision at 12 months in eyes treated with radiotherapy compared with no radiotherapy (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.64 to 1.04, 811 eyes, 8 studies, I2 = 66%, low-certainty evidence). Low-certainty evidence suggests a small benefit in change in visual acuity (mean difference (MD) -0.10 logMAR, 95% CI -0.17 to -0.03; eyes = 883; studies = 10) and average contrast sensitivity at 12 months (MD 0.15 log units, 95% CI 0.05 to 0.25; eyes = 267; studies = 2). Growth of new vessels (largely change in CNV size) was variably reported and It was not possible to produce a summary estimate of this outcome. The studies were small with imprecise estimates and there was no consistent pattern to the study results (very low-certainty evidence). Quality of life was only reported in one study of 199 people; there was no clear difference between treatment and control groups (low-certainty evidence). Low-certainty evidence was available on adverse effects from eight of 14 studies. Seven studies reported on radiation retinopathy and/or neuropathy. Five of these studies reported no radiation-associated adverse effects. One study of 88 eyes reported one case of possible radiation retinopathy. One study of 74 eyes graded retinal abnormalities in some detail and found that 72% of participants who had radiation compared with 71% of participants in the control group had retinal abnormalities resembling radiation retinopathy or choroidopathy. Four studies reported cataract surgery or progression: events were generally few with no consistent evidence of any increased occurrence in the radiation group. One study noted transient disturbance of the precorneal tear film but there was no evidence from the other two studies that reported dry eye of any increased risk with radiation therapy. None of the participants received anti-VEGF injections. Radiotherapy combined with anti-VEGF versus anti-VEGF alone People receiving radiotherapy/anti-VEGF were probably more likely to lose 3 or more lines of BCVA at 12 months compared with anti-VEGF alone (RR 2.11, 95% CI 1.40 to 3.17, 1050 eyes, 3 studies, moderate-certainty). Most of the data for this outcome come from two studies of epimacular brachytherapy (114 events) compared with 20 events from the one trial of EBM. Data on change in BCVA were heterogenous (I2 = 82%). Individual study results ranged from a small difference of -0.03 logMAR in favour of radiotherapy/anti-VEGF to a difference of 0.13 logMAR in favour of anti-VEGF alone (low-certainty evidence). The effect differed depending on how the radiotherapy was delivered (test for interaction P = 0.0007). Epimacular brachytherapy was associated with worse visual outcomes (MD 0.10 logMAR, 95% CI 0.05 to 0.15, 820 eyes, 2 studies) compared with EBM (MD -0.03 logMAR, 95% CI -0.09 to 0.03, 252 eyes, 2 studies). None of the included studies reported contrast sensitivity or quality of life. Growth of new vessels (largely change in CNV size) was variably reported in three studies (803 eyes). It was not possible to produce a summary estimate and there was no consistent pattern to the study results (very low-certainty evidence). For adverse outcomes, variable results were reported in the four studies. In three studies reports of adverse events were low and no radiation-associated adverse events were reported. In one study of epimacular brachytherapy there was a higher proportion of ocular adverse events (54%) compared to the anti-VEGF alone (18%). The majority of these adverse events were cataract. Overall 5% of the treatment group had radiation device-related adverse events (17 cases); 10 of these cases were radiation retinopathy. There were differences in average number of injections given between the four studies (1072 eyes). In three of the four studies, the anti-VEGF alone group on average received more injections (moderate-certainty evidence). AUTHORS' CONCLUSIONS: The evidence is uncertain regarding the use of radiotherapy for neovascular AMD. Most studies took place before the routine use of anti-VEGF, and before the development of modern radiotherapy techniques such as stereotactic radiotherapy. Visual outcomes with epimacular brachytherapy are likely to be worse, with an increased risk of adverse events,  probably related to vitrectomy. The role of stereotactic radiotherapy combined with anti-VEGF is currently uncertain. Further research on radiotherapy for neovascular AMD may not be justified until current ongoing studies have reported their results

Utilizing Targeted Gene Therapy with Nanoparticles Binding Alpha v Beta 3 for Imaging and Treating Choroidal Neovascularization

Purpose: The integrin αvβ3 is differentially expressed on neovascular endothelial cells. We investigated whether a novel intravenously injectable αvβ3 integrin-ligand coupled nanoparticle (NP) can target choroidal neovascular membranes (CNV) for imaging and targeted gene therapy. Methods: CNV lesions were induced in rats using laser photocoagulation. The utility of NP for in vivo imaging and gene delivery was evaluated by coupling the NP with a green fluorescing protein plasmid (NP-GFPg). Rhodamine labeling (Rd-NP) was used to localize NP in choroidal flatmounts. Rd-NP-GFPg particles were injected intravenously on weeks 1, 2, or 3. In the treatment arm, rats received NP containing a dominant negative Raf mutant gene (NP-ATPμ-Raf) on days 1, 3, and 5. The change in CNV size and leakage, and TUNEL positive cells were quantified. Results: GFP plasmid expression was seen in vivo up to 3 days after injection of Rd-NP-GFPg. Choroidal flatmounts confirmed the localization of the NP and the expression of GFP plasmid in the CNV. Treating the CNV with NP-ATPμ-Raf decreased the CNV size by 42% (P<0.001). OCT analysis revealed that the reduction of CNV size started on day 5 and reached statistical significance by day 7. Fluorescein angiography grading showed significantly less leakage in the treated CNV (P<0.001). There were significantly more apoptotic (TUNEL-positive) nuclei in the treated CNV. Conclusion: Systemic administration of αvβ3 targeted NP can be used to label the abnormal blood vessels of CNV for imaging. Targeted gene delivery with NP-ATPμ-Raf leads to a reduction in size and leakage of the CNV by induction of apoptosis in the CNV