Peripapillary microvasculature in the retinal nerve fiber layer in glaucoma by optical coherence tomography angiography: focal structural and functional correlations and diagnostic performance.

PURPOSE: To quantify peripapillary microvasculature within the retinal nerve fiber layer (RNFL) in primary open-angle glaucoma (POAG) and normal eyes, determine association of perfusion parameters with structural and functional measures, and report diagnostic accuracy of perfusion parameters. PATIENTS AND METHODS: POAG and normal patients underwent 6×6 mm2 optic nerve head scans (Angioplex optical coherence tomography angiography [OCTA]; Cirrus HD-OCT 5000) and Humphrey Field Analyzer II-i 24-2 visual field (VF) testing. Prototype software performed semiautomatic segmentation to create RNFL en face images and quantified vessel area density (VAD), vessel skeleton density (VSD), and vessel complexity index (VCI) in the optic nerve head globally and focally. Generalized estimating equations models assessed association of OCTA parameters with VF mean deviation (MD) and RNFL thickness. RESULTS: Thirty-eight POAG and 17 normal eyes were studied. Global VAD, VSD, and VCI were reduced in mild POAG vs normal (P<0.02) and moderate-severe vs mild POAG (P<0.04). Stepwise focal reductions across disease stage were demonstrated for OCTA parameters in the inferior hemisphere (P<0.05); reduction in OCTA parameters in mild POAG vs normal was demonstrated in inferior and superior quadrants (P<0.05). Reduced global VF MD was associated with reduced VAD, VSD, and VCI (P=0.0007, 0.0013, <0.0001; R 2=0.449, 0.312, 0.399, respectively), and global RNFL thickness was associated with VAD, VSD, and VCI (P<0.0001; R 2=0.499, 0.524, 0.542), superior and inferior hemifield MD were associated with corresponding VAD, VSD, and VCI (P≤0.001; R 2 from 0.208 to 0.513). RNFL thickness in all quadrants was associated with corresponding OCTA parameters (P<0.05; R 2 from 0.213 to 0.394), except temporal VAD and VCI. Area under curves for VAD, VSD, and VCI demonstrated good diagnostic ability (0.868, 0.855, 0.868; P<0.0001). CONCLUSION: Glaucomatous eyes showed stepwise reductions in RNFL microcirculation across severity; focal reductions in the inferior hemisphere and inferior and superior quadrants were most significant. OCTA parameters had stronger associations with structural rather than functional measures of glaucoma.

Structural and Functional Associations of Macular Microcirculation in the Ganglion Cell-Inner Plexiform Layer in Glaucoma Using Optical Coherence Tomography Angiography.

PURPOSE: To quantify retinal microvasculature within the macular ganglion cell-inner plexiform layer (GCIPL) in primary open-angle glaucoma (POAG) and normal eyes, determine association of vessel parameters with structural and functional measures, and report diagnostic accuracy of vessel parameters. METHODS: POAG and normal patients underwent 6×6 mm macula scans [Angioplex optical coherence tomography angiography (OCTA); Cirrus HD-OCT 5000]; and Humphrey Field Analyzer II-i 24-2 visual field (VF). Prototype software performed semiautomatic segmentation to create GCIPL en face images, and quantified vessel area density (VAD), vessel skeleton density (VSD), and vessel complexity index (VCI) for the macula (globally, hemifields, and 6 focal sectors). Linear regression assessed association of OCTA parameters with VF mean deviation (MD) and GCIPL thickness globally and focally. RESULTS: A total of 34 POAG and 21 normal eyes were studied. VAD, VSD, and VCI were reduced in POAG versus normal (0.463 vs. 0.486, P=0.00029; 0.230 vs. 0.219, P=0.0014; 1.15 vs. 1.09, P=0.0044, respectively), with a trend of worsening with increased POAG severity. Reduced global VF MD was associated with reduced VAD and VCI, controlling for age and intereye correlation (P=0.0060, 0.0080; R=0.205, 0.211). Both superior and inferior hemifield MD were associated with corresponding VAD, VSD, and VCI (all P<0.007; R ranged from 0.12 to 0.29). Global GCIPL thickness was not associated with global OCTA parameters, and only inferior sector GCIPL thickness was associated with corresponding VAD, VSD, and VCI (P<0.05; R ranged from 0.15 to 0.16). Area under curves for VAD, VSD, and VCI were fair to good (0.83, 0.79, 0.82; respectively; P<0.0001). CONCLUSIONS: Glaucomatous eyes had reduced GCIPL microcirculation. OCTA parameters had stronger associations with functional rather than structural measures of glaucoma. This observation deserves further study.

Rabbit model of ocular indirect photodynamic therapy using a retinoblastoma xenograft.

PURPOSE: The goal of this project was to demonstrate the feasibility of coupling the indirect ophthalmoscope laser delivery system with the 690 nm wavelength diode laser used to perform photodynamic therapy (PDT) in the treatment of retinoblastoma. METHODS: For phase 1, a total of six pigmented rabbits were treated with the indirect laser delivery system. The laser source was provided by the Lumenis Opal 690 nm laser unit, delivered through a 810 nm Indirect ophthalmoscope headpiece and a hand-held 28-diopter indirect lens (1.0 mm spot size). Four rabbits received intravenous verteporfin at doses of 0.43 or 0.86 mg/kg, and two rabbits did not receive verteporfin (controls). A second phase of the study involved eight rabbits using a retinoblastoma xenograft to determine the effect of indirect PDT on subretinal tumors. RESULTS: For phase 1, a total of 20 laser treatments were performed in the right eyes of six rabbits. Laser power levels ranged between 40 and 150 mW/cm2 and treatment duration ranged between 1 and 3 min. In the four rabbits that received verteporfin, focal retinal scars were noted at 40 mW/cm2 and higher power levels. In the two control rabbits that did not receive verteporfin, thermal burns were confirmed at 75 mW/cm2 and higher power levels. Histopathology showed focal retino-choroidal scars at the site of PDT treatment, without evidence of generalized ocular damage. Using the retinoblastoma xenograft, the indirect PDT system was shown to cause areas of tumor necrosis on histopathology. CONCLUSIONS: The results of this pre-clinical study suggest verteporfin may be activated in the rabbit retina with the indirect delivery system and the 690 nm laser unit (i.e., Indirect PDT). Using verteporfin, treatment effects were observed at 40-50 mW/cm2 in the rabbit retina, while photocoagulation was achieved at 75 mW/cm2 and higher power levels. Fundoscopic and histopathologic examination of treated areas showed circumscribed areas of retinal damage and a lack of generalized ocular toxicity, suggesting that this modality may represent a safe and localized method for treating intraocular retinoblastoma.

Clinical Significance of Optic Nerve Enhancement on Magnetic Resonance Imaging in Enucleated Retinoblastoma Patients.

PURPOSE: The aim of this 8-year retrospective review was to determine the clinical significance of gadolinium-enhanced magnetic resonance imaging (MRI) findings in retinoblastoma patients after enucleation, particularly the presence of abnormal contrast enhancement of the transected optic nerve. DESIGN: Retrospective chart review. SUBJECTS: A review was done on 88 patients with retinoblastoma undergoing 90 enucleations between January 2008 and December 2015. METHODS: These patients underwent 233 MRI scans: 90 preoperative and 143 postoperative that were included for review. MAIN OUTCOME MEASURE: The primary outcome measure assessed was abnormal MRI findings in the preoperative and postoperative MRI scans, specifically enhancement of the optic nerve and correlations between abnormal MRI findings and clinical outcomes for the 88 patients. RESULTS: On the preoperative MRI, 4 optic nerves out of 90 scans showed positive enhancement. Fifty orbits had ≥1 postoperative MRI. Overall, 41 of 50 orbits (82%) of enucleated patients demonstrated postoperative contrast enhancement on MRI after enucleation, at a mean interval of 10 months after surgery. The percentage of MRI scans with optic nerve enhancement was 77% from 0 to 6 months after enucleation and 68% at >24 months after surgery. Postenucleation optic nerve enhancement did not correlate with preoperative optic nerve enhancement, chemotherapy administration, or the presence of optic nerve invasion on histopathology. No child required an orbital biopsy. None of the 88 patients were found to have subsequent orbital or metastatic disease at the last clinical follow-up visit (average, 29 months; range, 1-71). CONCLUSION: Optic nerve contrast enhancement on follow-up MRI after enucleation for retinoblastoma seems to be a common, benign radiographic finding; none of the patients in this series developed extraocular tumor relapse. The presence of postenucleation enhancement on MRI did not correlate with preoperative chemotherapy or the presence of optic nerve invasion on histopathology. Based on our findings, intervention for isolated optic nerve enhancement on MRI is not indicated in the absence of other abnormal clinical or radiographic signs. A prospective trial with a validated radiographic grading system would be helpful to clarify the MRI features to differentiate orbital recurrence from benign postoperative enhancement.