The Role of Optical Coherence Tomography Angiography in Glaucoma.

Glaucoma is the leading cause of irreversible vision loss and comprises a group of chronic optic neuropathies characterized by progressive retinal ganglion cell (RGC) loss. Various etiologies, including impaired blood supply to the optic nerve, have been implicated for glaucoma pathogenesis. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality for visualizing the ophthalmic microvasculature. Using blood flow as an intrinsic contrast agent, it distinguishes blood vessels from the surrounding tissue. Vessel density (VD) is mainly used as a metric for quantifying the ophthalmic microvasculature. The key anatomic regions for OCTA in glaucoma are the optic nerve head area including the peripapillary region, and the macular region. Specifically, VD of the superficial peripapillary and superficial macular microvasculature is reduced in glaucoma patients compared to unaffected subjects, and VD correlates with functional deficits measured by visual field (VF). This renders OCTA similar in diagnostic capabilities compared to structural retinal nerve fiber layer (RNFL) thickness measurements, especially in early glaucoma. Furthermore, in cases where RNFL thickness measurements are limited due to artifact or floor effect, OCTA technology can be used to evaluate and monitor glaucoma, such as in eyes with high myopia and eyes with advanced glaucoma. However, the clinical utility of OCTA in glaucoma management is limited due to the prevalence of imaging artifacts. Overall, OCTA can play a complementary role in structural OCT imaging and VF testing to aid in the diagnosis and monitoring of glaucoma.

Clinical Course and Visual Outcomes of Papilledema in Pediatric Cerebral Venous Sinus Thrombosis.

PURPOSE: Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening event with significant neurologic and visual morbidity. In this study, we report on the natural history and visual outcomes of papilledema in children with CVST. DESIGN: Retrospective case series. METHODS: Patients with CVST evaluated by the Department of Ophthalmology between 2000 and 2023 were included. Records were reviewed for presence and course of papilledema, treatment, and final visual outcomes following papilledema resolution. RESULTS: The study included 35 patients with a mean age of 9 ± 5 years and 40% were female. The most common risk factors for CVST were infection (69%), dehydration (26%), and hypercoagulability (23%). 31 patients (89%) had papilledema. Of these patients, 9 (29%) had progression of papilledema despite treatment, 17 patients (55%) did not have progression, and 5 patients (16%) lacked follow-up records. Initial Frisén grade among all cases was 2 ± 1, and cases with progression reached a grade of 4 ± 1 between 10 and 32 days following initial identification. Most patients (97%) were treated with anticoagulation and 100% required acetazolamide and/or lumbar puncture. Among 26 patients with follow-up, papilledema resolved in 107 ± 128 days. Fifty-four percent of patients had permanent ophthalmic sequelae. An initial Frisén grade ≥3 (odds ratio 7.54, 95% confidence interval 6.53-8.70, P< .001) was significantly associated with eventual optic atrophy. CONCLUSIONS: Children with CVST are at high risk for ophthalmologic sequelae. Papilledema can progress despite appropriate therapy. Our results highlight the importance of ophthalmologic follow-up during treatment course to prevent irreversible vision loss.

Comparison of Structural and Functional Features in Primary Angle Closure and Open Angle Glaucomas.

PRCIS: Using a large data set, we showed structural and functional differences between primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG). Primary angle closure glaucoma has relative structural preservation and worse functional loss inferiorly. PURPOSE: To identify structural and functional differences in PACG and POAG. MATERIALS AND METHODS: In this large cross-sectional study, differences in structural and functional damage were assessed among patients with POAG and PACG with optical coherence tomography and reliable visual field testing. RESULTS: In all, 283 patients with PACG and 4110 patients with POAG were included. Despite similar mean deviation on visual fields (mean [SD] -7.73 [7.92] vs. -7.53 [6.90] dB, P =0.72), patients with PACG had thicker global retinal nerve fiber layer (RNFL), smaller cup volume, smaller cup-to-disc ratio, and larger rim area than POAG (77 [20] vs. 71 [14] µm, 0.32 [0.28] vs. 0.40 [0.29] mm 3 , 0.6 [0.2] vs. 0.7 [0.1], 1.07 [0.40] vs. 0.89 [0.30] mm 2 , P <0.001 for all), while patients with POAG had more pronounced inferior RNFL thinning (82 [24] vs. 95 [35] µm, P <0.001). In a multivariable analysis, hyperopia [odds ratio (OR): 1.24, confidence interval (CI): 1.13-1.37], smaller cup-to-disc ratio (OR: 0.69, CI: 0.61-0.78), thicker inferior RNFL (OR: 1.15, CI: 1.06-1.26) and worse mean deviation (OR: 0.95, CI: 0.92-0.98) were associated with PACG. Functionally, POAG was associated with superior paracentral loss and PACG with inferior field loss. After adjusting for average RNFL thickness, PACG was associated with more diffuse loss than POAG (total deviation differences 1.26-3.2 dB). CONCLUSIONS: Patients with PACG had less structural damage than patients with POAG despite similar degrees of functional loss. Regional differences in patterns of functional and structural loss between POAG and PACG may improve disease monitoring for these glaucoma subtypes.

Artifacts in OCT Retinal Nerve Fiber Layer Imaging in Patients with Boston Keratoprosthesis Type 1.

PURPOSE: To determine the clinical utility of OCT retinal nerve fiber layer (OCT RNFL) imaging for glaucoma evaluation in patients with Boston keratoprosthesis type 1 (KPro) by investigating imaging artifacts. DESIGN: Case-control study. SUBJECTS: Patients with KPro and without KPro (controls) matched for age, gender, and glaucoma diagnosis. METHODS: The most recent Cirrus OCT RNFL scan from 1 eye was categorized as having good signal strength (SS; ≥ 6 out of 10) or poor SS (< 6). Those with good SS were analyzed by 2 independent reviewers for artifacts. Images with good SS and no artifacts affecting the scanning circle were considered useful for glaucoma evaluation. MAIN OUTCOME MEASURES: The incidence of poor SS and artifacts in OCT RNFL images; patient characteristics associated with useful scans. RESULTS: Sixty-five patients with KPro and 75 controls were included; 89.2% of KPro patients and 89.3% of control subjects had glaucoma (P = 0.98). Forty percent of KPro patients and 5.3% of controls had poor SS (P < 0.001). The proportion of images with either poor SS or artifacts was similar in KPro (76.9%) vs. controls (72.0%, P = 0.51). The most common artifacts in both groups were missing data (43.6%, 53.2%, respectively, P = 0.32) and motion artifact (25.6%, 19.7%, respectively, P = 0.47). Images were useful for glaucoma evaluation in 43.1% of KPro patients and in 69.3% of controls (P = 0.002). In the KPro group, patients with useful OCT scans, compared with those without, had better visual acuity (0.4 ± 0.3 vs. 0.9 ± 0.7 logarithm of the minimum angle of resolution, P = 0.004), and did not have congenital corneal pathologies (0.0% vs. 24.3%, P = 0.008). A multivariate analysis showed that KPro patients with older age had higher odds of useful OCT images (odds ratio, 1.05; P = 0.03). Among KPro patients with useful OCT scans, retinal nerve fiber layer thickness correlated with observed cup-to-disc ratio (Pearson correlation: r = -0.42, P = 0.03). CONCLUSIONS: The rate of OCT RNFL images with either poor signal strength or artifacts in the KPro and control population was comparable. In patients with KPro, where intraocular pressure measurements are difficult and glaucoma is highly prevalent and often severe, OCT RNFL imaging can be useful for glaucoma evaluation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Artifact Correction in Retinal Nerve Fiber Layer Thickness Maps Using Deep Learning and Its Clinical Utility in Glaucoma.

Purpose: Correcting retinal nerve fiber layer thickness (RNFLT) artifacts in glaucoma with deep learning and evaluate its clinical usefulness. Methods: We included 24,257 patients with optical coherence tomography and reliable visual field (VF) measurements within 30 days and 3,233 patients with reliable VF series of at least five measurements over ≥4 years. The artifacts are defined as RNFLT less than the known floor value of 50 µm. We selected 27,319 high-quality RNFLT maps with an artifact ratio (AR) of <2% as the ground truth. We created pseudo-artifacts from 21,722 low-quality RNFLT maps with AR of >5% and superimposed them on high-quality RNFLT maps to predict the artifact-free ground truth. We evaluated the impact of artifact correction on the structure-function relationship and progression forecasting. Results: The mean absolute error and Pearson correlation of the artifact correction were 9.89 µm and 0.90 (P < 0.001), respectively. Artifact correction improved R2 for VF prediction in RNFLT maps with AR of >10% and AR of >20% up to 0.03 and 0.04 (P < 0.001), respectively. Artifact correction improved (P < 0.05) the AUC for progression prediction in RNFLT maps with AR of ≤10%, >10%, and >20%: (1) total deviation pointwise progression: 0.68 to 0.69, 0.62 to 0.63, and 0.62 to 0.64; and (2) mean deviation fast progression: 0.67 to 0.68, 0.54 to 0.60, and 0.45 to 0.56. Conclusions: Artifact correction for RNFLTs improves VF and progression prediction in glaucoma. Translational Relevance: Our model improves clinical usability of RNFLT maps with artifacts.

Association between HSP-Specific T-Cell Counts and Retinal Nerve Fiber Layer Thickness in Patients with Primary Open-Angle Glaucoma.

Objective: Previous laboratory reports implicate heat shock protein (HSP)-specific T-cell responses in glaucoma pathogenesis; here, we aimed to provide direct clinical evidence by correlating systemic HSP-specific T-cell levels with glaucoma severity in patients with primary open-angle glaucoma (POAG). Design: Cross-sectional case-control study. Subjects: Thirty-two adult patients with POAG and 38 controls underwent blood draw and optic nerve imaging. Methods: Peripheral blood monocytes (PBMC) were stimulated in culture with HSP27, α-crystallin, a member of the small HSP family, or HSP60. Both interferon-γ (IFN-γ)+ CD4+ T helper type 1 cells (Th1) and transforming growth factor-ß1 (TGF-ß1)+ CD4+ regulatory T cells (Treg) were quantified by flow cytometry and presented as a percentage of total PBMC counts. Relevant cytokines were measured using enzyme-linked immunosorbent assays. Retinal nerve fiber layer thickness (RNFLT) was measured with OCT. Pearson's correlation (r) was used to assess correlations. Main Outcome Measures: Correlations of HSP-specific T-cell counts, and serum levels of corresponding cytokine levels with RNFLT. Results: Patients with POAG (visual field mean deviation, -4.7 ± 4.0 dB) and controls were similar in age, gender, and body mass index. Moreover, 46.9% of POAG and 60.0% of control subjects had prior cataract surgery (P = 0.48). Although no significant difference in total nonstimulated CD4+ Th1 or Treg cells was detected, patients with POAG exhibited significantly higher frequencies of Th1 cells specific for HSP27, α-crystallin, or HSP60 than controls (7.3 ± 7.9% vs. 2.6 ± 2.0%, P = 0.004; 5.8 ± 2.7% vs. 1.8 ± 1.3%, P < 0.001; 13.2 ± 13.3 vs. 4.3 ± 5.2, P = 0.01; respectively), but similar Treg specific for the same HSPs compared with controls (P ≥ 0.10 for all). Concordantly, the serum levels of IFN-γ were higher in POAG than in controls (36.2 ± 12.1 pg/ml vs. 10.0 ± 4.3 pg/ml; P < 0.001), but TGF-ß1 levels did not differ. Average RNFLT of both eyes negatively correlated with HSP27- and α-crystallin-specific Th1 cell counts, and IFN-γ levels in all subjects after adjusting for age (partial correlation coefficient r = -0.31, P = 0.03; r = -0.52, p = 0.002; r = -0.72, P < 0.001, respectively). Conclusions: Higher levels of HSP-specific Th1 cells are associated with thinner RNFLT in patients with POAG and control subjects. The significant inverse relationship between systemic HSP-specific Th1 cell count and RNFLT supports the role of these T cells in glaucomatous neurodegeneration. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Glaucoma management in patients with penetrating keratoplasty or keratoprosthesis.

PURPOSE OF REVIEW: Advances in surgical techniques and postoperative care have significantly improved rates of short-term complications following keratoplasty; however, glaucoma remains a highly prevalent long-term and potentially devastating complication for postkeratoplasty patients. In this review, we provide an overview of recent literature on glaucoma management in patients who have undergone penetrating keratoplasty or the Boston keratoprosthesis type I (KPro) implantation. RECENT FINDINGS: New research suggests an inflammatory cause underlying glaucoma following KPro. Accurate IOP measurement is difficult in patients postkeratoplasty; study of objective techniques such as PDCT or Tono-Pen in penetrating keratoplasty eyes and trans-palpebral Diaton tonometry in KPro eyes have shown promising results. Early glaucoma surgical intervention should be considered for patients undergoing penetrating keratoplasty and KPro. SUMMARY: Patients who have undergone penetrating keratoplasty or implantation of the Boston keratoprosthesis type I should be monitored frequently for elevated intraocular pressure and for other signs of glaucomatous optic nerve damage. Intraocular pressure elevation should be treated promptly either medically or surgically while minimizing risk to the corneal graft. Further research into inflammatory causes and other treatment modalities is promising for the long-term visual success in these patients.

Magnetic resonance imaging, clinicopathologic findings, and clinical progression of a puppy with confirmed Eastern equine encephalitis virus.

A 5-month-old puppy was evaluated for rapidly progressive neurologic signs and pyrexia. Magnetic resonance imaging showed multifocal meningoencephalitis with transtentorial and foramen magnum herniation. A cerebrospinal fluid tap revealed highly cellular fluid, and the puppy was euthanized. Histopathology showed lymphoplasmacytic and neutrophilic meningoencephalitis. Viral polymerase chain reaction testing for Eastern equine encephalitis was positive. Rapid progression of neurologic signs and respiratory arrest necessitated mechanical ventilation. Severe hypernatremia, most consistent with central diabetes insipidus, developed. Key clinical message: Transtentorial and foramen magnum herniation and high cerebrospinal fluid cell counts may be indicators of poor prognosis. Brain death, respiratory arrest, and central diabetes insipidus may also ensue with Eastern equine encephalitis infection.

Imagerie par résonance magnétique, résultats clinicopathologiques et progression clinique d'un cas confirmé d'infection par le virus de l'encéphalite équine de l'Est chez un chiot. Un chiot de 5 mois a été évalué pour des signes neurologiques progressant rapidement et une pyrexie. L'imagerie par résonance magnétique a montré une méningo-encéphalite multifocale avec hernies transtentorielle et au foramen magnum. Un prélèvement de liquide céphalo-rachidien a révélé un liquide hautement cellulaire et le chiot a été euthanasié. L'histopathologie a montré une méningo-encéphalite lymphoplasmocytaire et neutrophilique. Un test de réaction en chaîne par la polymérase pour l'encéphalite équine de l'Est était positif. La progression rapide des signes neurologiques et l'arrêt respiratoire ont nécessité une ventilation mécanique. Une hypernatrémie sévère, plus compatible avec un diabète insipide central, s'est développée.Message clinique clé:Une hernie transtentorielle et au foramen magnum de même qu'un nombre élevé de cellules dans le liquide céphalorachidien peuvent être des indicateurs de mauvais pronostic. La mort cérébrale, l'arrêt respiratoire et le diabète insipide central peuvent également s'ensuivre avec une infection par l'encéphalite équine de l'Est.(Traduit par Dr Serge Messier).