RETINAL NEOVASCULARIZATION FROM A PATIENT WITH CUTIS MARMORATA TELANGIECTATICA CONGENITA.

PURPOSE: To report a rare case of peripheral retinal neovascularization in a patient diagnosed with cutis marmorata telangiectatica congenita (CMTC). METHODS: Observational case report. RESULTS: A 16-year-old girl was referred to clinic for retinal evaluation. The patient had a clinical diagnosis of CMTC later confirmed by skin biopsy. Examination revealed temporal peripheral retinal sheathing, as well as lattice degeneration in both eyes. Wide-field fluorescein angiogram showed substantive peripheral retinal nonperfusion with evidence of vascular leakage from areas of presumed retinal neovascularization. The patient subsequently had pan retinal photocoagulation laser treatment to each eye without complication. DISCUSSION: Cutis marmorata telangiectatica congenita is a rare vascular condition known to affect multiple organ systems including the eyes. Although ocular manifestations of CMTC are rare, instances of congenital glaucoma, suprachoroidal hemorrhage, and bilateral total retinal detachments resulting in secondary neovascular glaucoma have been reported. Our patient demonstrates the first reported findings of peripheral nonperfusion and retinal neovascularization related to CMTC in a 16-year-old girl. We propose early retinal examination, wide-field fluorescein angiogram, and early pan retinal photocoagulation laser treatment in patients with peripheral nonperfusion and retinal neovascularization from CMTC.

Adult Coats' Disease, Dubin-Johnson Syndrome, and the Search for Targeted Therapies.

Coats' disease is nonhereditary retinal vascular disorder characterized by telangiectatic retinal vessels with prominent aneurysmal changes and exudation. A conclusive etiology has not yet been determined. In this retrospective case report and literature review, a 64-year-old male with Dubin-Johnson syndrome presented with unilateral retinal vascular changes and exudation consistent with a diagnosis of adult Coats' disease. The authors conclude that patients with Dubin-Johnson syndrome carry mutations in a multidrug resistance associated protein (MRP). MRPs are also expressed in the retina, retinal pigment epithelium, and vascular endothelium, where they export toxins and metabolites, and may serve as a therapeutic target. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:318-321.].

Optical coherence tomography angiography features in patients with idiopathic full-thickness macular hole, before and after surgical treatment.

PURPOSE: To present optical coherence tomography (OCT) angiography features in patients with idiopathic full-thickness macular hole before and after vitrectomy. STUDY DESIGN: Prospective case series study. MATERIALS AND METHODS: Patients presenting with an idiopathic full-thickness macular hole (IMH) who underwent posterior vitrectomy with internal limiting membrane peeling and gas tamponade were included in the study. En face OCT and OCT angiography (OCTA) was performed pre- and postoperatively using 3×3 mm scans (Optovue, XR Avanti). Foveal avascular zone (FAZ) area, macular hole size (MHS), central retinal thickness (CRT), macular parafoveal choriocapillary flow area (MCFA), and fovea vessel density (FVDS) were measured and assessed using OCTA. Best-corrected visual acuity (BCVA) was examined before and 3 months after surgery. RESULTS: Twenty-eight eyes of 28 patients were included in the study. The mean age of patient group was 68.28 years. The hole was closed in all eyes after the initial surgery. OCTA showed enlargement of FAZ and increased CRT in foveal area. Mean preoperative FAZ area was 0.39±0.07 mm2. En face images of the middle retina showed a range of preoperative cystic patterns surrounding the hole. BCVA was improved from 0.1±0.11 preoperatively to 0.42±0.17 postoperatively. Mean FAZ area was reduced to 0.24±0.07 mm2 postoperatively with resolution of macular hole and adjacent cystic areas. Mean CRT was reduced from 396±62.6 µm pre-operatively to 272±30.7 µm postoperatively. After vitrectomy, the parafoveal choriocapillary flow area and FVDS of IMH eyes increased compared with the preoperative measurements. CONCLUSION: Quantitative evaluation of vascular and morphological changes following IMH surgery using OCTA shows the potential for recovery due to vascular and neuronal plasticity. OCTA showing vascular changes and their quantitative characteristics might be a useful tool for the assessment of macular holes before and after surgical treatment.

EyeSAM: graph-based localization and mapping of retinal vasculature during intraocular microsurgery.

PURPOSE: Robot-assisted intraocular microsurgery can improve performance by aiding the surgeon in operating on delicate micron-scale anatomical structures of the eye. In order to account for the eyeball motion that is typical in intraocular surgery, there is a need for fast and accurate algorithms that map the retinal vasculature and localize the retina with respect to the microscope. METHODS: This work extends our previous work by a graph-based SLAM formulation using a sparse incremental smoothing and mapping (iSAM) algorithm. RESULTS: The resulting technique, "EyeSAM," performs SLAM for intraoperative vitreoretinal surgical use while avoiding spurious duplication of structures as with the previous simpler technique. The technique also yields reduction in average pixel error in the camera motion estimation. CONCLUSIONS: This work provides techniques to improve intraoperative tracking of retinal vasculature by handling loop closures and achieving increased robustness to quick shaky motions and drift due to uncertainties in the motion estimation.

Design and evaluation of a new bioelectrical impedance sensor for micro-surgery: application to retinal vein cannulation.

PURPOSE: Nowadays, millions of people suffer from retinal vein occlusion, a blind-making eye disease. No curative treatment currently exists for this vascular disorder. However, a promising treatment consists in injecting a thrombolytic drug directly inside the affected retinal vessel. Successfully puncturing miniature vessels with diameters between 50 and 400 [Formula: see text] remains a real challenge, amongst others due to human hand tremor, poor visualisation and depth perception. As a consequence, there is a significant risk of double-puncturing the targeted vessel. Sub-surfacic injection of thrombolytic agent could potentially lead to severe retinal damage. METHODS: A new bio-impedance sensor has been developed to visually display the instant of vessel puncture. The physical working principle of the sensor has been analysed, and a representative electrical model has been derived. Based on this model, the main design parameters were derived to maximise the sensor sensitivity. A detailed characterisation and experimental validation of this concept were conducted. RESULTS: Stable, repeatable and robust impedance measurements were obtained. In an experimental campaign, 35 puncture attempts on ex vivo pig eyes vessels were conducted. A confusion matrix shows a detection accuracy of 80% if there is a puncture, a double puncture or no puncture. The 20% of inaccuracy most probably comes from the limitations of the employed eye model and the experimental conditions. CONCLUSIONS: The developed bio-impedance sensor has shown great promise to help in avoiding double punctures when cannulating retinal veins. Compared to other puncture detection methods, the proposed sensor is simple and therefore potentially more affordable. Future research will include validation in an in vivo situation involving vitreoretinal surgeons.

Two-Year Efficacy of Ranibizumab Plus Laser-Induced Chorioretinal Anastomosis vs Ranibizumab Monotherapy for Central Retinal Vein Occlusion: A Randomized Clinical Trial.

Importance: Adding a laser-induced chorioretinal anastomosis (L-CRA) to current treatments for central retinal vein occlusion (CRVO) may improve outcomes and lessen therapy burdens. Objective: To determine the 2-year efficacy of intravitreal ranibizumab with an L-CRA vs ranibizumab alone for patients with macular edema caused by CRVO. Design, Setting, and Participants: In this randomized clinical trial conducted at a single university clinic from March 2012 to June 2015, 58 participants with macular edema caused by CRVO were randomized 1:1 to either an L-CRA or sham procedure at baseline. All participants received monthly intravitreal injections of ranibizumab, 0.5 mg. Data were analyzed from April 2017 to September 2017. Interventions: Random assignment to L-CRA plus monthly injections of intravitreal ranibizumab, 0.5 mg, (combination group; n = 29) or to a sham L-CRA procedure plus monthly injections of intravitreal ranibizumab, 0.5 mg, (ranibizumab alone group; n = 29) for 6 months. From month 7 to month 24, participants were evaluated monthly and received an injection of ranibizumab if a loss of 5 or more letters of best-corrected visual acuity (BCVA) on ETDRS chart from previous highest score occurred or if there was evidence of residual macular edema on optical coherence tomography. Main Outcomes and Measures: Mean number of injections from month 7 to month 24, change in BCVA, and change in central subfield thickness (CST). Results: Of the 58 included participants, 38 (66%) were men, and the mean (SD) age was 68.6 (11.8) years; participants had a mean (SD) BCVA of 57.09 (11.87) ETDRS letters (Snellen equivalent, 20/73) and a mean (SD) CST of 738.36 (175.54) µm. A successful L-CRA was created in 24 of 29 participants (83%) in the combination group. The mean number of injections from month 7 to month 24 was 3.2 (95% CI, 2.5-3.8) in the combination group and 7.1 (95% CI, 6.0-8.0) in the ranibizumab alone group. The ratio of the number of injections in the combination group compared with the ranibizumab alone group was 0.46 (95% CI, 0.36-0.61; P < .001). Mixed-effects regression modeling showed a difference in mean BCVA at 2 years between the combination and ranibizumab alone groups (combination, 70.3 letters [Snellen equivalent, 20/40]; ranibizumab alone, 61.6 letters [Snellen equivalent, 20/60]; difference, 8.8 letters; 95% CI, 0.2-17.3; P = .05). There was also a difference in CST at 2 years between the combination and ranibizumab alone groups (mean CST: combination, 303.6 µm; ranibizumab alone, 394.5 µm; difference, 90.9 µm; 95% CI, 24.3-157.5; P = .01). Four participants (14%) in the combination group required a vitrectomy for early macular traction or vitreous hemorrhage. Conclusions and Relevance: For macular edema caused by CRVO, an L-CRA significantly reduced the number of ranibizumab injections required. Trial Registration: anzctr.org.au Identifier: ACTRN12612000004864.

Frosted branch angiitis with penetrating ocular trauma and retained intraocular foreign body.

A 54-year-old male sustained ocular trauma with a projectile. Examination of the right eye revealed an intraocular foreign body (IOFB) adjacent to the optic nerve head, vitritis, vitreous hemorrhage, and translucent perivascular sheathing of the retinal vessels in all quadrants suggesting frosted branch angiitis (FBA). The patient underwent vitrectomy with removal of the IOFB and silicone oil tamponade under steroid cover. With continued use of systemic and topical steroids after surgery, complete resolution of FBA and improvement in vision were noted in a week. Prompt resolution of FBA after IOFB removal points toward a strong association between the presence of IOFB and FBA.

EyeSLAM: Real-time simultaneous localization and mapping of retinal vessels during intraocular microsurgery.

BACKGROUND: Fast and accurate mapping and localization of the retinal vasculature is critical to increasing the effectiveness and clinical utility of robot-assisted intraocular microsurgery such as laser photocoagulation and retinal vessel cannulation. METHODS: The proposed EyeSLAM algorithm delivers 30 Hz real-time simultaneous localization and mapping of the human retina and vasculature during intraocular surgery, combining fast vessel detection with 2D scan-matching techniques to build and localize a probabilistic map of the vasculature. RESULTS: In the harsh imaging environment of retinal surgery with high magnification, quick shaky motions, textureless retina background, variable lighting and tool occlusion, EyeSLAM can map 75% of the vessels within two seconds of initialization and localize the retina in real time with a root mean squared (RMS) error of under 5.0 pixels (translation) and 1° (rotation). CONCLUSIONS: EyeSLAM robustly provides retinal maps and registration that enable intelligent surgical micromanipulators to aid surgeons in simulated retinal vessel tracing and photocoagulation tasks.

Successful Complete Revascularization With PCI Using Super-Low Volume of Contrast Medium in a Patient With Three-Vessel Disease Including 2 Chronic Total Occlusions With Severe Renal Dysfunction.

The most important factor for preventing contrast-induced nephropathy (CIN) during percutaneous coronary intervention (PCI) in patients with severe renal dysfunction is to minimize the contrast volume. Herein, we report a successful case of complete revascularization after 3 separate PCI procedures using a super-low volume of contrast medium in a patient with 3-vessel disease, including two chronic total occlusions (CTOs). A 70-year-old man having exertional angina despite maximal medical therapy was referred to our hospital. He had severe renal dysfunction (estimated glomerular filtration rate 19 mL/minute/1.73 m2). Coronary angiography, in which a total volume of 15 mL (over 3 injections) of contrast medium was used after hydration with normal saline, demonstrated 2 CTOs in the proximal left circumflex artery (LCX) and the proximal right coronary artery (RCA) as well as focal stenosis in the mid left descending artery (LAD). Because the patient refused coronary artery bypass grafting, we opted for revascularization with PCI, divided into 3 procedures. We made full use of microcatheter tip injection and evaluation with intravascular ultrasound and achieved complete revascularization with a total of 31 mL of contrast medium: 9 mL for RCA, 6 mL for LAD, and 16 mL for LCX, without the occurrence of CIN. Additionally, we present tips for performing PCI using super-low contrast medium.

Feasibility study on robot-assisted retinal vascular bypass surgery in an ex vivo porcine model.

PURPOSE: To describe a new robot-assisted surgical system for retinal vascular bypass surgery (RVBS) and to compare the success rate with freehand RVBS. METHODS: A robot-assisted system for retinal microsurgery was constructed to include two independent robotic arms. A 23-gauge light probe and an intraocular forceps were affixed to the arm end effectors to perform the intraocular manipulation. Harvested porcine eyes were introduced to be established animal models of closed-sky eyeballs after that pars plana vitrectomy using temporary keratoprosthesis was performed by a skilful surgeon. Retinal vascular bypass surgery (RVBS) was performed by an inexperienced ophthalmologist to test the ease of use. A stainless steel wire (45-µm pipe diameter) was used as an artificial vessel. Before RVBS, the wires were prepositioned at the retinal surface of the eyes. The Control group (n = 20) underwent freehand RVBS, and the Experimental group (n = 20) underwent robot-assisted RVBS. To create the simulated bypass, the distal end of the wire was inserted into the selected vessel and advanced ~4 mm away from the optic disc. If successful, then the proximal wire end was inserted and advanced ~2 mm towards the optic disc. The difference in the success rate for the freehand and robot-assisted procedures was analysed by the chi-square test. RESULTS: The success rate for the freehand RVBS was 5% (1/20 eyes). In contrast, the robot-assisted success rate was 35% (7/20) of eyes (p < 0.05). CONCLUSION: This study demonstrated the feasibility of robot-assisted RVBS in ex vivo porcine eyes. The robotic system increased the accuracy and stability of manipulation by eliminating freehand tremor, leading to a higher surgical success rate.

Effect of leaking perifoveal microaneurysms on resolution of diabetic macular edema treated by combination therapy using anti-vascular endothelial growth factor and short pulse focal/grid laser photocoagulation.

PURPOSE: The effect of combination therapy using intravitreal ranibizumab (IVR) injections and short pulse focal/grid laser photocoagulation was evaluated for the treatment of diabetic macular edema (DME). METHODS: The current investigation was a preliminary single-arm, open-label, prospective clinical study conducted on 21 eyes at 4 sites in Japan. Treatment protocol consisted of two phases. The induction IVR phase included two monthly IVRs followed by PRN IVR phase in which additional IVR was administered if the central macular thickness (CMT) exceeded 300 µm. One week after each IVR in both phases, short pulse focal/grid laser was delivered to treat residual leakage outside of the fovea (>500 µm) and reduce edema fluid influx. At the 6-month endpoint, the effects of treatment were examined in terms of best corrected visual acuity (BCVA), CMT, and required number of IVR injections in eyes with or without perifoveal leaking microaneurysms (MAs). RESULTS: In eyes with initial BCVA ≤70 letters, mean BCVA was significantly ameliorated by 7.0 ± 7.4 letters (P = 0.0324) and mean CMT improved significantly by 174.8 ± 105.0 µm (P = 0.0005). Both BCVA improvement (P = 0.8693) and CMT reduction (P = 0.9336) were comparable between MA(-) and MA(+) groups. The MA(-) group required significantly fewer PRN-IVR injections than did the MA(+) group over the 6-month study period (mean 3.4 ± 1.6 vs. 5.3 ± 0.9, median 3.0 vs. 5.5; P = 0.0229). CONCLUSIONS: Short pulse focal/grid laser photocoagulation could reduce the number of IVR injections required to resolve macular edema and increase BCVA in a possible mechanism of reduced influx of edema fluid into the foveal area in eyes without apparent perifoveal microaneurysms.

Indocyanine-green-guided targeted laser photocoagulation of capillary macroaneurysms in macular oedema: a pilot study.

AIMS: In longstanding diabetic macular oedema (DME) or retinal vein occlusion (RVO), capillary macroaneurysms may develop. Indocyanine green angiography (ICGA) has been shown to optimise their detection. Here, we report the anatomical and functional outcome of the elective photocoagulation of capillary macroaneurysms. METHODS: A retrospective, interventional, two-centre study. In eyes with chronic macular oedema and severe hard exsudates due to diabetic retinopathy or RVO, the presence of capillary macroaneurysms (defined by a diameter larger than 150 µm) was assessed by ICGA and optical coherence tomography (OCT). Capillary macroaneurysms were selectively photocoagulated, the presence of photothrombosis within the lumen being assessed by immediate OCT. RESULTS: Four eyes from three patients with DME and five eyes from five patients with RVO were included. The median duration of visual loss was 4 years. Median initial visual acuity (VA) was 20/200. The median number of capillary macroaneurysms per eye was 2 (range, 1-8) and their median size was 410 µm (range, 154-603). Six months after photocoagulation, there was a significant reduction in macular thickness (mean±SD, 528 µm±200 vs 271 µm±152, p<0.05) and improvement of VA (mean log MAR, 0.82 vs 0.58, p<0.05). CONCLUSIONS: During macular oedema with severe hard exsudates due to DME or RVO, systematic detection of capillary macroaneurysms by ICGA followed by their OCT-controlled photocoagulation may be of interest. These results may contribute to re-evaluate the role of photocoagulation in the management of longstanding macular oedema.

Surgically induced changes in retinal vessel diameter, retinal nerve fibre layer thickness, and the optic disc after 23-gauge pars plana vitrectomy.

The aim of the study is to investigate the retinal vascular calibre, retinal nerve fibre layer's thickness, and optic disc changes in patients after pars plana vitrectomy. We examined 40 eyes in 40 patients who had undergone unilateral pars plana vitrectomy at three time points: prior to surgery, and at 3 and 6 months after the operation. The diameters of central retinal arteries and veins were measured using retinal photographs. The central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were calculated using the revised Parr-Hubbard formula. Retinal nerve fibre layer thickness was obtained using Stratus optical coherence tomography. The cup-to-disc vertical ratio of the optic disc was evaluated using stereo optic disc photography. There were no significant differences between the eyes of individual patients before the operation. Cup-to-disc vertical ratios of the optic disc were significantly increased 3 and 6 months postoperatively (p < 0.01, p < 0.01), and there was a significant difference between the operative eye and fellow eye at the same time points (p < 0.01, p < 0.01). Changes in CRAE and CRVE in the operative eyes were significantly larger than the fellow eyes 6 months postoperatively (p < 0.01, p < 0.01). The retinal nerve fibre layer thickness showed no significant changes. While there were no changes in retinal nerve fibre layer thickness, vitrectomy induced changes in the cup-to-disc vertical ratio of the optic disc and retinal vessel diameter for at least 6 months after surgery.

A Computational Model of Peripheral Photocoagulation for the Prevention of Progressive Diabetic Capillary Occlusion.

We developed a computational model of the propagation of retinal ischemia in diabetic retinopathy and analyzed the consequences of various patterns and sizes of burns in peripheral retinal photocoagulation. The model addresses retinal ischemia as a phenomenon of adverse local feedback in which once a capillary is occluded there is an elevated probability of occlusion of adjacent capillaries resulting in enlarging areas of retinal ischemia as is commonly seen clinically. Retinal burns of different sizes and patterns, treated as local oxygen sources, are predicted to have different effects on the propagation of retinal ischemia. The patterns of retinal burns are optimized with regard to minimization of the sum of the photocoagulated retina and computer predicted ischemic retina. Our simulations show that certain patterns of retinal burns are effective at preventing the spatial spread of ischemia by creating oxygenated boundaries across which the ischemia does not propagate. This model makes no statement about current PRP treatment of avascular peripheral retina and notes that the usual spot sizes used in PRP will not prevent ischemic propagation in still vascularized retinal areas. The model seems to show that a properly patterned laser treatment of still vascularized peripheral retina may be able to prevent or at least constrain the propagation of diabetic retinal ischemia in those retinal areas with intact capillaries.

Intravitreal bevacizumab and feeder vessel laser treatment for a posteriorly located retinal capillary hemangioma.

Retinal capillary hemangioma (RCH) is strongly associated with von Hippel-Lindau (VHL) disease. Treatment of this sight-threatening condition is often unsatisfactory despite multiple treatment options available. We here describe an interesting case of a 50-year-old male with RCH located in the perifoveal region of the left eye. Subretinal bleed, exudation, and macular edema resulted in progressive deterioration of visual acuity. Fundus photography, fluorescein angiography, and optical coherence tomography (OCT) were used to serially monitor the lesion. After ruling out systemic lesions of VHL disease, the patient was subjected to direct laser photocoagulation of the lesion which resulted in further loss in vision with increase in bleed and exudation. Subsequently, the patient was given 2 monthly intravitreal injections of bevacizumab followed by laser photocoagulation of feeder arteriole. This combination therapy resulted in resolution of exudation, bleed, and macular edema with improvement in visual acuity. Thus, vision-threatening RCH may be safely and effectively treated by means of a combination therapy comprising of intravitreal bevacizumab and feeder vessel treatment.

FEEDER VESSEL LASER PHOTOCOAGULATION FOR IDIOPATHIC, SUBFOVEAL POLYPOIDAL CHOROIDAL VASCULOPATHY NOT RESPONDING TO EITHER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY OR PHOTODYNAMIC THERAPY.

PURPOSE: To describe the management of a subfoveal polypoidal choroidal vasculopathy case refractory to antiangiogenic treatment and to photodynamic therapy. METHODS: Case report. A 65-year-old male patient presented with a diagnosis of exudative age-related macular degeneration of his left eye and unsuccessful response to eight antiangiogenic injections. Visual acuity was 20/33. Fluorescein angiography, spectral domain optical coherence tomography, and indocyanine green angiography confirmed the diagnosis of polypoidal choroidal vasculopathy. Two photodynamic therapy sessions along with two ranibizumab injections were performed, but no response was obtained. Identification and photocoagulation of the polyp feeder vessels was performed. RESULTS: Polypoidal structures regressed, intraretinal and subretinal exudation resolved, and visual acuity was preserved with no adverse events. CONCLUSION: Indocyanine green angiography-guided feeder vessel diode laser photocoagulation in selected cases of polypoidal choroidal vasculopathy may be considered an effective alternative therapy, especially in those refractory to both photodynamic therapy and antiangiogenic therapy.

Comparative efficacy of pure yellow (577-nm) and 810-nm subthreshold micropulse laser photocoagulation combined with yellow (561-577-nm) direct photocoagulation for diabetic macular edema.

PURPOSE: To compare the efficacy of 577- and 810-nm subthreshold micropulse laser photocoagulation (SMLP) combined with direct photocoagulation to microaneurysms in diabetic macular edema (DME). METHODS: A prospective nonrandomized interventional case series. Forty-nine consecutive patients (53 eyes) with DME were recruited. In 20/24 (83.3%) eyes, 810-nm SMLP (810-nm MP) to achieve a confluent grid pattern was followed by direct photocoagulation to microaneurysms via a continuous 561-nm wavelength laser. In 21/29 (72.5%) eyes, 577-nm SMLP (577-nm MP) was combined with direct photocoagulation to microaneurysms via the same instrument. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were examined 1, 2, 3, 6 and 12 months after treatment. RESULTS: The mean power required for SMLP was lower in the 577-nm than in the 810-nm MP group (204.1 vs. 954.1 mW) (p < 0.0001). Significant reductions in CMT persisted from 3 to 12 months after treatment in all patients (p < 0.01). There were no significant intergroup differences in CMT until 12 months. In both groups, mean BCVA remained stable until 12 months after treatment. Additional treatment for persistent macular edema was performed within 12 months in 4/24 eyes (16.7%) in the 810-nm MP group and 1/29 eyes (3.4%) in the 577-nm MP group. CONCLUSION: Either 577-nm MP or 810-nm MP combined with direct photocoagulation for microaneurysm closure reduced DME, maintained visual acuity and reduced the additional treatment rate within 12 months. The 577-nm MP apparatus required less energy for SMLP than the 810-nm MP instrument and was suitable for direct photocoagulation of microaneurysms.