Bibiana J. Reiser

Optimal wavelength for ultrahigh-resolution optical coherence tomography

The influence of depth dependent dispersion by the main component of biological tissues, water, on the resolution of OCT was studied. Investigations showed that it was possible to eliminate the influence of depth dependent dispersion by water in tissue by choosing a light source with a center wavelength near 1.0 microm. Ultrahigh resolution ophthalmic imaging was performed at this wavelength range with a microstructure fiber light source.

Keratoconus Diagnosis with Optical Coherence Tomography Pachymetry Mapping

OBJECTIVE To detect abnormal corneal thinning in keratoconus using pachymetry maps measured by high-speed anterior segment optical coherence tomography (OCT). DESIGN Cross-sectional observational study. PARTICIPANTS Thirty-seven keratoconic eyes from 21 subjects and 36 eyes from 18 normal subjects. METHODS The OCT system operated at a 1.3 microm wavelength with a scan rate of 2000 axial scans per second. A pachymetry scan pattern (8 radials, 128 axial scans each; 10 mm diameter) centered at the corneal vertex was used to map the corneal thickness. The pachymetry map was divided into zones by octants and annular rings. Five pachymetric parameters were calculated from the region inside the 5 mm diameter: minimum, minimum-median, inferior-superior (I-S), inferotemporal-superonasal (IT-SN), and the vertical location of the thinnest cornea. The 1-percentile value of the normal group was used to define the diagnostic cutoff. Placido-ring-based corneal topography was obtained for comparison. MAIN OUTCOME MEASURES The OCT pachymetric parameters and a quantitative topographic keratoconus index (keratometry, I-S, astigmatism, and skew percentage [KISA%]) were used for keratoconus diagnosis. Diagnostic performance was assessed by the area under the receiver operating characteristic (AROC) curve. RESULTS Keratoconic corneas were thinner. The pachymetric minimum averaged 452.6+/-60.9 microm in keratoconic eyes versus 546+/-23.7 microm in normal eyes. The 1-percentile cutoff was 491.6 microm. The thinnest location was inferiorly displaced in keratoconus (-805+/-749 microm vs -118+/-260 microm; cutoff, -716 microm). The thinning was focal (minimum-median: -95.2+/-41.1 microm vs -45+/-7.7 microm; cutoff, -62.6 microm). Keratoconic maps were more asymmetric (I-S, -44.8+/-28.7 microm vs -9.9+/-9.3 microm; cutoff, -31.3 microm; and IT-SN, -63+/-35.7 microm vs -22+/-11.4 microm; cutoff, -48.2 microm). Keratoconic eyes had a higher KISA% index (2641+/-5024 vs 21+/-19). All differences were statistically significant (t test, P<0.0001). Applying the diagnostic criteria of any 1 OCT pachymetric parameter below the keratoconus cutoff yielded an AROC of 0.99, which was marginally better (P = .09) than the KISA% topographic index (AROC, 0.91). CONCLUSIONS Optical coherence tomography pachymetry maps accurately detected the characteristic abnormal corneal thinning in keratoconic eyes. This method was at least as sensitive and specific as the topographic KISA. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Microglial stability and repopulation in the retina.

Background/aims: Parenchymal central nervous system microglia are repopulated by bone marrow derived monocytes more slowly than any other reticuloendothelial cells. The contribution of bone marrow derived monocytes to the uninflammed retina has not been studied. The present study sought to determine repopulation of retinal microglia in uniflammed retina by bone marrow derived monocytes in bone marrow chimeric rats. Methods: Chimeric (Y→X) Lewis rats were constructed by transplanting 5×107 male bone marrow cells into lethally irradiated female recipient rats. The chimeras were sacrificed 8, 10, 12, 30, and 52 weeks after bone marrow transplant, and retina, brain, lung, and spleen samples were collected. DNA was extracted and quantified. Y positive infiltrating cells in the collected samples were detected by polymerase chain reaction amplification of a Y chromosome specific 104 bp fragment. Results: There was a rapid repopulation of haematopoietic tissues in the spleen (at 8 weeks), confirming the establishment of chimerism, and to a lesser extent, of lung (at 30 weeks). This repopulation was absent in the brain parenchyma and retina until 52 weeks after transplantation. Conclusions: These data indicate that resident microglia in the retina, much like those in the brain, are stable in number in the retinal compartment (up to 1 year), and repopulation by bone marrow derived cells may be delayed for a year.

Association of herpesviruses in the aqueous humor of patients with serpiginous choroiditis: a polymerase chain reaction-based study.

Purpose: To determine the presence of herpesvirus DNA in the aqueous humor (AH) of patients with serpiginous choroiditis using polymerase chain reaction (PCR). Methods: AH from nine patients previously diagnosed with serpiginous choroiditis were investigated for herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) by conventional virological methods and PCR. The PCR-positive DNA was gel-purified, extracted, and sequenced using a dye-based Applied Biosystems procedure. The sequences were processed through the National Cancer Institute’s BLAST inquiry for species identification. Results: Culture and cytological examination of AH from all nine patients were negative for HSV,VZV, and CMV. Five were positive for VZV, one was positive for HSV, and three were wholly negative using PCR. Subsequent DNA sequencing of the positive samples authenticated the presence of VZV and HSV DNA in the respective patients. Conclusion: VZV and HSV DNA were detected in a subset of patients with serpiginous choroiditis, suggesting that these viruses may function in the pathogenesis of this disease.

Fluoroquinolone therapy in Mycobacterium chelonae keratitis after lamellar keratectomy

Purpose: To characterize a rabbit model of Mycobacterium chelonae keratitis after lamellar keratectomy and assess the effectiveness of fluoroquinolone therapy. Setting: University Laboratory, University of California, Irvine, California, USA. Methods: Twenty‐eight New Zealand white rabbits had unilateral lamellar keratectomy with placement of 2.5 × 105 colony‐forming units of log‐phase M chelonae under each flap. Eyes (7 per group) were randomized and treated with sterile balanced salt solution, gatifloxacin 0.3%, ciprofloxacin 0.3%, or levofloxacin 0.5% 4 times daily. Two masked observers examined all eyes on days 2, 5, and 7 and weekly for 4 weeks. Severity of disease and bacterial culture results were the main outcomes measured. The means and standard deviations were calculated, and differences between the groups were statistically analyzed. Results: All eyes developed clinical disease. At the time the rabbits were killed, eyes treated with balanced salt solution, ciprofloxacin, levofloxacin, and gatifloxacin were culture positive in 6 (85.7%), 7 (100%), 6 (85.7%), and 3 (42.9%) of 7 eyes per group, respectively. Frequency of positive culture and the severity of clinical disease in gatifloxacin‐treated eyes were significantly less (P<.05) than in the other groups combined. Conclusions: The rabbit model of M chelonae keratitis was successfully developed in our study. A fourth‐generation quinolone (gatifloxacin) showed the best performance among the fluoroquinolones tested in our experimental approach. The fourth‐generation fluoroquinolone, gatifloxacin, could be effectively used for the treatment of mycobacterial keratitis.

A novel characterization of posterior keratoconus using anterior segment optical coherence tomography in an infant: a case report

BackgroundPosterior keratoconus is a rare cause of a corneal opacity in an infant. It is characterized by thinning of the posterior cornea without ectasia of the anterior cornea. Imaging of this condition with anterior segment optical coherence tomography (AS-OCT) has not been reported in the literature.Case presentationA six week old African-American male presented with a congenital corneal opacity of the right eye. He underwent an examination under anesthesia in which photography and AS-OCT were performed. AS-OCT confirmed the diagnosis of posterior keratoconus. The patient subsequently underwent an optical iridectomy for visual development.ConclusionAS-OCT is a useful tool in cases when a child presents with a corneal opacity of unknown or unclear etiology. In our patient, AS-OCT showed the classic description of central corneal thinning seen in this condition. Additionally, it revealed an associated detached Descemet membrane, a feature which has not been previously described in posterior keratoconus.

Genomic cfDNA Analysis of Aqueous Humor in Retinoblastoma Predicts Eye Salvage: The Surrogate Tumor Biopsy for Retinoblastoma

Tumor-derived cell-free DNA (cfDNA) has biomarker potential; therefore, this study aimed to identify cfDNA in the aqueous humor (AH) of retinoblastoma eyes and correlate somatic chromosomal copy-number alterations (SCNA) with clinical outcomes, specifically eye salvage. AH was extracted via paracentesis during intravitreal injection of chemotherapy or enucleation. Shallow whole-genome sequencing was performed using isolated cfDNA to assess for highly recurrent SCNAs in retinoblastoma including gain of 1q, 2p, 6p, loss of 13q, 16q, and focal MYCN amplification. Sixty-three clinical specimens of AH from 29 eyes of 26 patients were evaluated; 13 eyes were enucleated and 16 were salvaged (e.g., saved). The presence of detectable SCNAs was 92% in enucleated eyes versus 38% in salvaged eyes (P = 0.006). Gain of chromosome 6p was the most common SCNA found in 77% of enucleated eyes, compared with 25% of salvaged eyes (P = 0.0092), and associated with a 10-fold increased odds of enucleation (OR, 10; 95% CI, 1.8–55.6). The median amplitude of 6p gain was 1.47 in enucleated versus 1.07 in salvaged eyes (P = 0.001). The presence of AH SCNAs was correlated retrospectively with eye salvage. The probability of ocular salvage was higher in eyes without detectable SCNAs in the AH (P = 0.0028), specifically 6p gain. This is the first study to correlate clinical outcomes with SCNAs in the AH from retinoblastoma eyes, as such these findings indicate that 6p gain in the aqueous humor is a potential prognostic biomarker for poor clinical response to therapy. Implications: The correlation of clinical outcomes and SCNAs in the AH identified in the current study requires prospective studies to validate these finding before SCNAs, like 6p gain, can be used to predict clinical outcomes at diagnosis. Mol Cancer Res; 16(11); 1701–12. ©2018 AACR.

Ophthalmic imaging in children: current practice patterns and perceived barriers

Pediatric ophthalmologists were surveyed to determine current practice patterns regarding ophthalmic imaging for children and to identify perceived barriers to the adoption of imaging technologies in their practices. Some form of imaging was available in the majority of practices (94%), but its use varied widely among different clinical scenarios. The two most frequently perceived barriers to performing imaging in children were cooperation and lack of sufficient data supporting ophthalmic imaging in clinical practice.