Angiographic features and disease outcomes of symptomatic retinal arterial macroaneurysms.

PURPOSE: Symptomatic retinal arterial macroaneurysms (RAM) are primarily investigated by fundus fluorescein angiography after presenting with visual disturbance. The natural history includes spontaneous regression and occasionally occlusion of the arteriole distal to the aneurysm. RAM may be managed conservatively. Interventional treatment options include focal argon laser photocoagulation, Nd:YAG laser hyaloidotomy, and pars plana vitrectomy. The purpose of this study was to elicit the rates of distal vessel occlusion and aneurysm thrombosis in RAM at presentation, and their relevance to the treatment of RAM. Furthermore, visual outcomes were examined. METHODS: Retrospective review of cases of RAM presenting to a tertiary ophthalmology care centre was accomplished in a university teaching hospital. The angiographic features, treatment indications, and visual outcomes in patients with RAM were recorded. Angiographic features noted were distal vessel patency and aneurysm thrombosis at presentation. RESULTS: Ten patients with RAM were identified. Ninety percent had an angiographically patent distal arteriole, with 40 % showing spontaneous thrombosis of the aneurysm sac at presentation. Patients presenting with a spontaneously thrombosed RAM were managed conservatively, those with flow within the aneurysm wall were treated with focal laser, and those with subhyaloid haemorrhage underwent Nd:YAG laser hyaloidotomy. LogMAR visual acuity improved from 0.3 (±0) at presentation to 0.15 (±0.1) in the conservative group, and from 0.78 (±0.23) to 0.24 (±0.18) in those who underwent one intervention. One patient lost vision after multiple RAM. CONCLUSION: Thrombosis within the aneurysm wall is an important feature in deciding to treat RAM, and selective use of interventions improves vision in affected patients.

Surgery for idiopathic full-thickness macular holes within four months of symptom onset yields superior visual outcomes: Results from an Irish patient cohort.

PURPOSE: To describe the anatomical, visual, and safety results of full-thickness macular hole (FTMH) repair surgery and determine factors influencing outcomes. PATIENTS AND METHODS: A retrospective chart review was performed on all patients who underwent primary FTMH repair surgery by a single surgeon over a 3-year period. For comparisons, Snellen visual acuity (VA) was converted to logMAR equivalent. Anatomical hole closure, visual improvement, and final VA of ≤ 0.30 logMAR were the primary outcome measures. RESULTS: Twenty eyes of 19 patients were included. Mean patient age was 69 years (range 55 to 80 years) and 74% were female. Mean minimum linear diameter (MLD) was 440 µm (range 170 µm to 1200 µm). Mean duration of symptoms before surgery was 16 weeks (range 3 to 39 weeks). 100% of eyes achieved successful anatomical FTMH closure. Mean VA improved from 1.03 ± 0.43 logMAR (Snellen 6/60) preoperatively to 0.35 ± 0.22 logMAR (Snellen 6/15) postoperatively (p = 0.0001). Patients with worse preoperative VA gained more vision than those with better preoperative VA (p = 0.01). Eyes operated on within 4 months of symptom onset were more than twice as likely to achieve a postoperative VA of ≤ 0.30 logMAR (Snellen 6/12 or better) compared to eyes with a longer duration of symptoms (p = 0.03). CONCLUSION: FTMH repair surgery was safe and effective, with outcomes comparing favourably with published international studies. All patients benefited from surgery regardless of symptom duration, presenting VA or FTMH size. However, surgery performed within 4 months of symptom-onset was particularly beneficial, highlighting the need for prompt referral and surgery.

Early vitrectomy is indicated for both diffuse and dense vitreous haemorrhages of unknown aetiology.

BACKGROUND: Early vitrectomy for complete fundus-obscuring vitreous haemorrhage (VH) allows for prompt diagnosis and treatment of the cause. AIMS: To analyse the causes of VH of unknown aetiology, whether partially fundus-obscuring or dense, and to determine the outcomes of early vitrectomy. METHODS: A retrospective review of patients who underwent early vitrectomy within 10 days of symptom-onset for partially fundus-obscuring or dense VH of unknown origin. Patients with evidence of proliferative diabetic retinopathy in either eye or any other preoperatively diagnosed aetiology of VH were excluded. RESULTS: 19 patients were included. Intraoperative diagnoses were: retinal tears without rhegmatogenous retinal detachment (RRD) (53%); peripheral localised RRD (32%); neovascularisation secondary to retinal vein occlusion (11%) and posterior vitreous detachment without a retinal break (5%). Patients with diffuse VH were as likely to have a retinal tear diagnosed as those with dense VH (88% vs 82%, respectively; p = 0.7). Mean VA improved from 1.26 LogMAR to 0.23 LogMAR postoperatively (p = 0.001). 1 patient (5%) developed a RRD one-year postoperatively. CONCLUSIONS: In cases of diffuse or dense VH of unknown aetiology, an occult retinal tear should be suspected. Early vitrectomy should be strongly considered regardless of whether the fundal view is partially or completely obscured, to prevent progression to visually significant RRDs.

Early Subretinal Allograft Rejection Is Characterized by Innate Immune Activity.

Successful subretinal transplantation is limited by considerable early graft loss despite pharmacological suppression of adaptive immunity. We postulated that early innate immune activity is a dominant factor in determining graft survival and chose a nonimmunosuppressed mouse model of retinal pigment epithelial (RPE) cell transplantation to explore this. Expression of almost all measured cytokines by DH01 RPE cells increased significantly following graft preparation, and the neutrophil chemoattractant KC/GRO/CINC was most significantly increased. Subretinal allografts of DH01 cells (C57BL/10 origin) into healthy, nonimmunosuppressed C57BL/6 murine eyes were harvested and fixed at 1, 3, 7, and 28 days postoperatively and subsequently cryosectioned and stained. Graft cells were detected using SV40 large T antigen (SV40T) immunolabeling and apoptosis/necrosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Sections were also immunolabeled for macrophage (CD11b and F4/80), neutrophil (Gr1 Ly-6G), and T-lymphocyte (CD3-ɛ) infiltration. Images captured with an Olympus FV1000 confocal microscope were analyzed using the Imaris software. The proportion of the subretinal bolus comprising graft cells (SV40T+) was significantly (p < 0.001) reduced between postoperative day (POD) 3 (90 ± 4%) and POD 7 (20 ± 7%). CD11b+, F4/80+, and Gr1 Ly-6G+ cells increased significantly (p < 0.05) from POD 1 and predominated over SV40T+ cells by POD 7. Colabeling confocal microscopic analysis demonstrated graft engulfment by neutrophils and macrophages at POD 7, and reconstruction of z-stacked confocal images confirmed SV40T inside Gr1 Ly-6G+ cells. Expression of CD3-ɛ was low and did not differ significantly between time points. By POD 28, no graft cells were detectable and few inflammatory cells remained. These studies reveal, for the first time, a critical role for innate immune mechanisms early in subretinal graft rejection. The future success of subretinal transplantation will require more emphasis on techniques to limit innate immune-mediated graft loss, rather than focusing exclusively on suppression of the adaptive immune response.

Preparation of pre-confluent retinal cells increases graft viability in vitro and in vivo: a mouse model.

PURPOSE: Graft failure remains an obstacle to experimental subretinal cell transplantation. A key step is preparing a viable graft, as high levels of necrosis and apoptosis increase the risk of graft failure. Retinal grafts are commonly harvested from cell cultures. We termed the graft preparation procedure "transplant conditions" (TC). We hypothesized that culture conditions influenced graft viability, and investigated whether viability decreased following TC using a mouse retinal pigment epithelial (RPE) cell line, DH01. METHODS: Cell viability was assessed by trypan blue exclusion. Levels of apoptosis and necrosis in vitro were determined by flow cytometry for annexin V and propidium iodide and Western blot analysis for the pro- and cleaved forms of caspases 3 and 7. Graft viability in vivo was established by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cleaved caspase 3 immunolabeling of subretinal allografts. RESULTS: Pre-confluent cultures had significantly less nonviable cells than post-confluent cultures (6.6%±0.8% vs. 13.1%±0.9%, p<0.01). Cell viability in either group was not altered significantly following TC. Caspases 3 and 7 were not altered by levels of confluence or following TC. Pre-confluent cultures had low levels of apoptosis/necrosis (5.6%±1.1%) that did not increase following TC (4.8%±0.5%). However, culturing beyond confluence led to progressively increasing levels of apoptosis and necrosis (up to 16.5%±0.9%). Allografts prepared from post-confluent cultures had significantly more TUNEL-positive cells 3 hours post-operatively than grafts of pre-confluent cells (12.7%±3.1% vs. 4.5%±1.4%, p<0.001). Subretinal grafts of post-confluent cells also had significantly higher rates of cleaved caspase 3 than pre-confluent grafts (20.2%±4.3% vs. 7.8%±1.8%, p<0.001). CONCLUSION: Pre-confluent cells should be used to maximize graft cell viability.