Unexplained Vision Loss Associated With Intraocular Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment Repair.

Purpose: To evaluate the visual outcomes with unexplained vision loss during or after silicone oil (SO) tamponade. Methods: This multicenter retrospective case series comprised patients with unexplained vision loss associated with SO tamponade or its removal. Eyes with other clear secondary identifiable causes of vision loss were excluded. Results: Twenty-nine eyes of 28 patients (64% male) were identified. The mean age was 50 ± 13 years (range, 13-78 years). The mean duration of SO tamponade was 148 ± 38 days. Eighteen eyes (62%) developed unexplained vision loss while under SO; 11 (38%) had vision loss after SO removal. The most common optical coherence tomography (OCT) finding was ganglion cell layer (GCL) thinning (55%). Eyes with vision loss after SO removal had a mean logMAR best-corrected visual acuity (BCVA) of 0.6 ± 0.7 (Snellen 20/85) before SO tamponade and 1.2 ± 0.4 (20/340) before SO removal. By the last follow-up after SO removal, the BCVA had improved to 1.1 ± 0.4 (20/235). In eyes with vision loss after SO removal, the BCVA before SO removal was 0.7 ± 0.7 (20/104), which deteriorated to 1.4 ± 0.4 (20/458) 1 month after SO removal. By the last follow-up, the BCVA had improved to 1.0 ± 0.5 (20/219). Conclusions: Unexplained vision loss can occur during SO tamponade or after SO removal. Vision loss was associated with 1000-centistoke and 5000-centistoke oil and occurred in macula-off and macula-on retinal detachments. The duration of tamponade was 3 months or longer in the majority of eyes. Most eyes had GCL thinning on OCT. Gradual visual recovery can occur yet is often incomplete.

Cataract Formation Following Pars Plana Vitrectomy in the Pediatric Population.

PURPOSE: To analyze post-vitrectomy cataract formation in the pediatric population to elucidate the number of phakic children requiring cataract surgery following vitreous surgery and the perioperative factors affecting cataract development in these patients. METHODS: Eyes of pediatric patients that underwent phakic pars plana vitrectomy (PPV) with no prior cataract in a 10-year period were included. Analyses evaluated relationships between patient age and time to cataract surgery, as well as contributing factors for cataract formation. Final visual outcomes were also examined. Outcomes were collected for patient age at first vitrectomy, indication for vitrectomy, use of tamponade agents, history of ocular trauma, cataract status, and time to cataract surgery from first vitrectomy. RESULTS: Of 44 eyes analyzed, 27 (61%) were noted to have some degree of cataract formation. Of these, 15 (56%; 34% of total eyes) underwent cataract surgery. Use of octafluoropropane (P = .04) or silicone oil (P = .03) positively correlated with the need for cataract surgery in the total study group. Patients requiring cataract surgery had worse endpoint visual acuities than those who did not undergo surgery (P = .02), although this difference becomes less significant in follow-up over 2 years (P = .30). Patients who had cataracts but did not need cataract surgery showed an improvement in visual acuity (P = .04), but this was not demonstrated in patients who did need cataract surgery (P = .90). CONCLUSIONS: Pediatric eye care providers should be aware of the significant risk of cataract formation following a phakic PPV. [J Pediatr Ophthalmol Strabismus. 2023;60(6):421-426.].

Using optical coherence tomography angiography as a biomarker of retinopathy severity and treatment for diabetic retinopathy.

Purpose: The goal was to evaluate optical coherence tomography angiography (OCT-A) as a biomarker to correlate retinal vessel density (VD) with diabetic retinopathy (DR) severity and visual acuity, as well as track antivascular endothelial growth factor (VEGF) treatment efficacy. Methods: This retrospective cohort study analyzed the automatically quantified VDs of the superficial vascular complex (SVC) and deep vascular complex (DVC), including the whole, foveal, and parafoveal VDs, on quality OCT-A scans in patients diagnosed with DR. A multivariate linear regression and analysis of variance (ANOVA) analysis compared VDs to DR severity, visual acuity, and demographic factors. A linear mixed analysis determined the effects of VD by whether anti-VEGF therapy was given to patients with OCT-A scans at multiple time points. Results: There was a positive correlation of the VDs in both the SVC whole and parafoveal VD and DVC parafoveal VD with decreased DR severity and increased visual acuity (p≤0.001). The DVC whole VD was also positively correlated with increased visual acuity (p<0.001). There was no difference in the VDs associated with anti-VEGF treatment over time. Conclusions: OCT-A VD shows promise for diagnosing and monitoring DR using DR severity and visual acuity. Anti-VEGF treatment had no significant effect (p=0.063) on vascular density in diabetic retinopathy.

Modeling of external self-excitation and force generation on magnetic nanoparticles inside vitreous cavity.

The purpose of this manuscript was to design a better method for recovery from rhegmatogenous retinal detachment (RRD) surgery. We attempted to achieve this by designing a helmet that can manipulate intraocular magnetic nanoparticles (MNPs) and create a magnetic tamponade, eliminating the need for postoperative head positioning. A simulated analysis was developed to predict the pattern of magnetic force applied to the magnetic nanoparticles by external magnetic field. No participants were involved in this study. Instead, magnetic flux and force data for three different helmet designs were collected using virtual simulation tools. A prototype helmet was then constructed and magnetic flux and force data were recorded and compared to virtual data. For both virtual and physical scenarios, magnitude and direction of the resulting forces were compared to determine which design created the controlled direction and strongest forces into the back of the eye. Of the three virtual designs, both designs containing a visor had greater force magnitude than magnet alone. Between both designs with visors, the visor with bends resulted in forces more directed at the back of the eye. The physical prototype helmet shared similar measurements to virtual simulation with minimal percent error (Average = 5.47%, Standard deviation = 0.03). Of the three designs, the visor with bends generated stronger forces directed at the back of the eye, which is most appropriate for creating a tamponade on the retina. We believe that this design has shown promising capability for manipulating intraocular MNPs for the purpose of creating a tamponade for RRD.

Reactivation of Retinopathy of Prematurity Three Years After Treatment With Bevacizumab.

Although intravitreal injection of anti-vascular endothelial growth factor agents (IVA) can induce rapid regression of retinopathy of prematurity (ROP), late reactivation of the ROP can occur in the form of tractional retinal detachment (TRD) from contracted recurrent extraretinal fibrovascular proliferation. The authors report a case of bilateral TRD for recurrent ROP in a 3-year-old, which is the latest-reported reactivation to date. The authors propose that persistent avascular retina in eyes that have undergone IVA for ROP receive laser ablation to prevent late recurrences. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:255-259.].

Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and immune rejection in murine corneal allograft model.

Although corneal allotransplantation is performed in the immune-privileged cornea, many grafts are still rejected after transplantation. This study examined the role of chemokine receptor D6 expression in a corneal allograft rejection, investigated the modulation of D6 expression in cells, and determined the effect of D6 on graft survival. Interestingly, D6 was highly expressed in CD45 -: cells and the corneal epithelium of accepted corneal allografts. From the mouse corneal allograft model, TGF-ß was found to play a key role in D6 up-regulation, leading to reduced CCL2, CCL5, and CCL3. To modulate D6 chemokine binding, a D6MT was developed and showed effective chemokine trapping through SPR and FACS assays. By treating corneal allografts with D6MT, the allograft survival rate was improved, and (lymph) angiogenesis was reduced. Direct allosensitization and DC LN homing was drastically reduced in the mouse corneal allograft model. These findings suggest that TGF-ß is a positive regulator of D6 expression, and it is a potential therapeutic target to enhance the survival of corneal allografts.

Nerves and neovessels inhibit each other in the cornea.

PURPOSE: To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea. METHODS: b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epithelium-derived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining. RESULTS: No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5% reduction, P = 0.001) and PEDF protein expression (64% reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed. CONCLUSION: Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis.

b-FGF induces corneal blood and lymphatic vessel growth in a spatially distinct pattern.

PURPOSE: To study the spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by basic fibroblast growth factor (b-FGF). METHODS: b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of Balb/c mice. On days 1, 3, and 7, blood (heme-) and lymphangiogenesis were observed by immunofluorescence staining of corneal flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels, respectively. A second group of corneas were harvested for quantitative real-time polymerase chain reaction. Each cornea was divided into 2 different areas: (1) pre-pellet area and (2) opposite-pellet area. Expression of vascular endothelial growth factor (VEGF) ligands was evaluated using real-time polymerase chain reaction in each respective zone. RESULTS: Blood vessels grew into the cornea from the pre-pellet area, whereas corneal lymphatic vessels grew from the opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in the pre-pellet, whereas VEGF-D expression was mostly observed in the opposite-pellet area. VEGF-C level increased simultaneously in both areas. CONCLUSIONS: A single inducing factor, that is, b-FGF, may simultaneously provoke hemangiogenesis and lymphangiogenesis in different locations of the cornea through differential expression of VEGF ligands. This distinctive spatial pattern should be considered while evaluating the corneal predilection for inflammation beyond that which is directly visible by slit lamp examination.

Vascular endothelial growth factor-C promotes alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis.

PURPOSE: To investigate the role of anti-vascular endothelial growth factor (VEGF)-C therapy in corneal graft survival and concomitant suppression of hem- and lymph-angiogenesis. METHODS: Corneal suture model in BALB/c mice was placed and immunohistochemical staining was performed with CD31/PECAM-1 and LYVE-1 to quantify the level of blood and lymphatic vessels. Corneal transplants were done in BALB/c mice from C57BL/6 mice donors; grafts were subsequently scored for opacity. VEGF-C was blocked in the angiogenesis and transplant model using neutralizing monoclonal anti-VEGF-C (VGX-100) by intraperitoneal injection. To determine the function of VEGF-C in maturation of antigen-presenting cells (APCs), bone marrow-derived dendritic cells were generated and matured in the presence or absence of VEGF-C. RESULTS: VEGF-C expression was demonstrated to be markedly upregulated in corneal graft rejection. VEGF-C blockade, through administration of a VEGF-C blocking monoclonal antibody, suppresses corneal angiogenic responses, inhibits trafficking and maturation of APCs, and significantly improves allotransplant survival. CONCLUSIONS: These data suggest VEGF-C as a potentially important target in corneal transplant pharmacotherapy and immunobiology.

Effects of topical and subconjunctival bevacizumab in high-risk corneal transplant survival.

PURPOSE: To investigate whether corneal graft survival could be improved by topical or subconjunctival bevacizumab in a murine model of vascularized high-risk corneal transplantation. METHODS: Before corneal transplantation, intrastromal sutures were placed for 2 weeks in the corneas of BALB/c mice, inducing intense angiogenesis. Allogeneic corneal transplantation was performed using C57BL/6 donor mice. Topical bevacizumab (2.5%) was delivered 3 times a day for 3 weeks in one treatment group, and 0.02 mL (0.5 mg) bevacizumab was injected subconjunctivally at days 0, 4, 8, and 15 after transplantation in the other treatment group. The control group received no treatment. Grafts were examined twice a week for 8 weeks by slit-lamp microscopy and were photographed once a week by slit-lamp digital camera and scored for opacity. For assessment of corneal neovascularization (NV), a quantitative method was used to measure three primary metrics including neovascular area, vessel caliber, and neovessel invasion area. RESULTS: Both topical and subconjunctival bevacizumab treatment reduced neovascular area and vessel caliber; however, the regression of corneal NV was more profound when treated subconjunctivally. The mean percentage reduction of neovascular area was 55% (P < 0.05) by week 8 in the subconjunctival treatment group and 33% (P = 0.15) in the topical group. Only subconjunctival bevacizumab treatment resulted in significant regression of neovessel invasion area (P < 0.05). All corneal transplants in both the control and the topical groups were rejected by 4 weeks after transplantation. However, in the subconjunctival treatment group, 33% of corneal grafts survived (P < 0.01). CONCLUSIONS: Subconjunctival bevacizumab may offer an adjunctive measure to conventional therapies in preventing graft rejection in high-risk corneal transplantation.