SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS OF RETINAL HYPERPERMEABILITY AND CHOROIDAL INFLAMMATION AS PREDICTORS OF SHORT-TERM FUNCTIONAL AND ANATOMICAL OUTCOMES IN EYES WITH DIABETIC MACULAR EDEMA TREATED WITH INTRAVITREAL BEVACIZUMAB.

PURPOSE: To assess spectral domain optical coherence tomography biomarkers of short-term outcomes in eyes with diabetic macular edema treated with intravitreal bevacizumab. METHODS: In a prospective interventional case series, 66 eyes with diabetic macular edema underwent 3 monthly intravitreal bevacizumab injections. Best-corrected visual acuity measurement and spectral domain optical coherence tomography were performed at baseline and at 3 months. Multivariate regression analysis was performed to investigate the baseline spectral domain optical coherence tomography parameters as predictors of functional and anatomical outcomes. RESULTS: Patients with diabetic nephropathy had greater subfoveal choroidal thickness (300.8 ± 35.54 vs. 253.0 ± 50.07 µm, P < 0.01) and were more likely to have subretinal fluid (r = 0.26, P = 0.03) at baseline. Multivariate analysis showed that the extent of external limiting membrane disruption (P = 0.03) and the extent of disorganization of retinal inner layers (P = 0.03) at baseline were predictors of best-corrected visual acuity at 3 months, whereas the extent of disorganization of retinal inner layers (P = 0.04) and duration of diabetes mellitus (P = 0.03) were predictors of central subfield thickness at 3 months. CONCLUSION: External limiting membrane disruption and disorganization of retinal inner layers, as the spectral domain optical coherence tomography biomarkers of retinal hyperpermeability, can predict short-term outcomes in diabetic macular edema eyes treated with intravitreal bevacizumab.

Ruthenium-106 plaque radiotherapy for uveal melanoma: analysis of tumor dimension and location on anatomical and functional results.

BACKGROUND: To report the long-term outcomes of Ru-106 plaque radiotherapy in eyes with uveal melanoma (UM) and to assess the effect of tumor thickness and location on final outcomes. METHODS: Medical records of 234 patients undergoing Ru-106 plaque radiotherapy for UM were reviewed, and the visual outcome, globe preservation, and patient survival were evaluated. The results of 2 groups were compared: 1. between thin (small and medium-sized, thickness < 7 mm, 148 eyes [63.2%]) and thick (thickness ≥ 7 mm, 86 eyes [36.8%]) tumors, and 2. between large (largest basal diameter [LBD] > 12 mm, 109 eyes [46.6%]) and medium/small (LBD ≤ 12 mm, 125 eyes [53.4%]). In addition, a comparison of the juxtapapillary location in 46 eyes (19.7%) versus tumors arising elsewhere and between tumors with and without ciliary involvement in 48 eyes (21.5%) were done. RESULTS: The patients were followed for a median of 54.2 months (range: 6-194.5 months). After adjusting for baseline visual acuity (VA), there was no significant association between final VA and different dimension and tumor location groups. Final globe preservation was 91.9%, and there was no significant difference between different dimension- and ciliary body involvement groups regarding anatomical success rate. The juxtapapillary tumors had lower globe preservation (80.4% vs .94.7%, p = 0.002). The hazard ratio (HR) for enucleation in juxtapapillary tumors was HR = 6.58 (95-CI: 3.84 to 11.21). The overall metastasis rate was 6.8%, with no significant difference in juxtapapillary tumors (4.3% vs.7.4%, p = 0.455). CONCLUSIONS: Ru-106 plaque radiotherapy is an effective treatment for thick and large UM. With this type of treatment, the globe preservation rate is lower in juxtapapillary tumors, but there is no significant difference in the metastasis rate.

ASSOCIATION OF VITREORETINAL LYMPHOMA WITH SYSTEMIC LYMPHOMA.

PURPOSE: To determine the association between vitreoretinal lymphoma and systemic lymphoma (SL). METHODS: Single-center retrospective review of medical records. RESULTS: Of 95 patients with vitreoretinal lymphoma, 18 (19%) had associated SL (SL group) and 77 (81%) were not associated with SL (no SL group). The most common sites of SL were skin (n = 5), testis (n = 2), liver and breast (n = 2), and others (n = 9). A comparison (SL group vs. [vs.] no SL group) revealed no difference in demographic or ocular findings at initial visit. In the SL group, SL occurred before the onset of ocular symptoms in 14 (78%) patients with mean interval of 86 months (median 61, range 5-286 months) or after ocular symptoms in 4 (22%) patients with mean interval of 19 months (median 12, range 7-44 months). A comparison revealed no difference in overall frequency of pre-existing or eventual central nervous SL (50% vs. 53%, P = 0.99); however, the SL group demonstrated central nervous SL more often after onset of ocular symptoms (78% vs. 17%, P = 0.001). A comparison found no difference in treatment methods, response of vitreoretinal lymphoma to treatment, final visual outcome, or death rate. CONCLUSION: We found 19% of patients with vitreoretinal lymphoma demonstrate related SL, and there was no difference in demographics, clinical features, or response to treatment, compared to those not associated with SL.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES OF VITREORETINAL LYMPHOMA IN 55 EYES.

PURPOSE: To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL). METHODS: Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019. RESULTS: There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression. CONCLUSION: Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.

PHOTODYNAMIC THERAPY FOR EXTRAFOVEOLAR CHOROIDAL OSTEOMA.

PURPOSE: To evaluate the outcome of photodynamic therapy (PDT) in the management of extrafoveolar choroidal osteoma. METHODS: The authors performed a retrospective chart review of all patients with choroidal osteoma that did not involve the foveola and were treated with standard-fluence PDT. RESULTS: Nine eyes with extrafoveolar choroidal osteoma were studied. Mean logarithm of the minimum angle of resolution best-corrected visual acuity at initial examination was 0.07 (Snellen ∼20/25). The osteoma was treated with 1 (8/9) or 2 (1/9) PDT sessions using 50 J/cm. After a mean follow-up of 49 months, the treated area of osteoma demonstrated complete (4/9) or partial (5/9) regression, with a mean of 73% regression in the PDT-treated areas. Tumor growth in the region of PDT was noted in 3 cases (3/9) (one tumor toward the foveola and two tumors at the margin away from the foveola), but in no case did the tumor reach the foveola. Therefore, PDT controlled tumor growth in 8 of 9 cases with only 1 of 9 cases showing growth through the PDT scar into foveola. Mean logarithm of the minimum angle of resolution visual acuity at last follow-up was 0.04 (Snellen ∼20/20) (P = 0.59). CONCLUSION: Photodynamic therapy is an effective modality for the management of extrafoveolar choroidal osteoma, minimizing tumor growth toward the foveola and preserving visual acuity.

Impact of uveal melanoma thickness on post-plaque radiotherapy outcomes in the prophylactic anti-vascular endothelial growth factor era in 1131 patients.

IMPORTANCE: The impact of tumour thickness on radiation complications following plaque radiotherapy for uveal melanoma in the anti-vascular endothelial growth factor (VEGF) era remains unknown. BACKGROUND: To evaluate treatment outcomes following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma based on initial tumour thickness. DESIGN: This was a retrospective, interventional case series. PARTICIPANTS: Patients with uveal melanoma were included in this study. METHODS: A review of medical records was conducted of patients with uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab from 7 July 2000 to 2 November 2018. MAIN OUTCOMES MEASURES: Radiation-related outcomes of cystoid macular oedema (CME), radiation maculopathy, papillopathy, retinopathy, iris neovascularization (NVI) and neovascular glaucoma (NVG) were compared based on tumour thickness (small [<3.0 mm] vs medium [3.1-8.0 mm] vs large [>8.0 mm]). RESULTS: Of 1131 eyes, 341 (30%) had small, 633 (56%) medium and 157 (14%) large melanoma. Comparison (small vs medium vs large) at 4 years following radiotherapy revealed large melanoma with greater Kaplan-Meier estimated risk of CME (37% vs 37% vs 63%, P < .001), earlier onset of CME (33 vs 26 vs 19 months, P < .001) and greater development of NVI (<1% vs 2% vs 13%, P < .001) and NVG (1% vs 2% vs 12%, P < .001). Radiation-induced maculopathy, papillopathy and retinopathy were not associated with tumour thickness. CONCLUSIONS AND RELEVANCE: Compared with small and medium uveal melanoma, large uveal melanoma demonstrated greater 48-month risk for CME, shorter time to CME onset and greater development of NVI and NVG following plaque radiotherapy and prophylactic intravitreal bevacizumab.

Genetic Analysis of Uveal Melanoma in 658 Patients Using the Cancer Genome Atlas Classification of Uveal Melanoma as A, B, C, and D.

PURPOSE: The Cancer Genome Atlas (TCGA) classification has been validated for uveal melanoma (UM) prognostication. We applied TCGA classification to UM biopsied using fine-needle aspiration biopsy (FNAB) to determine the predictability for metastasis and death. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with UM treated with plaque radiotherapy at Wills Eye Hospital, Philadelphia, Pennsylvania, from October 1, 2008, through December 31, 2018, who completed genetic analysis of chromosomes 3 and 8 after FNAB. METHODS: Tumors were classified as A, B, C, or D and were compared using the chi-square test, Fisher exact test, analysis of variance, and Kaplan-Meier analysis. MAIN OUTCOME MEASURES: Metastasis and death. RESULTS: Six hundred fifty-eight UM patients were categorized accordingly as TCGA class A (n = 342 [52%]), B (n = 91 [14%]), C (n = 118 [18%]), and D (n = 107 [16%]). More advanced tumor classification revealed older mean patient age (56 vs. 53 vs. 60 vs. 63 years, respectively; P < 0.001), worse presenting visual acuity (20/20-20/50: 81% vs. 67% vs. 71% vs. 66%, respectively; P < 0.001), greater distance from the optic disc (3.5 vs. 4.9 vs. 5.7 vs. 5.3 mm, respectively; P < 0.001), larger tumor basal diameter (10.3 vs. 12.9 vs. 13.9 vs. 15.3 mm, respectively; P < 0.001), and greater tumor thickness (4.3 vs. 6.1 vs. 6.6 vs. 7.5 mm, respectively; P < 0.001). After mean follow-up (47.6 vs. 47.6 vs. 42.9 vs. 28.7 months, respectively; P < 0.001), more advanced TCGA class was associated with increased risk of metastasis (3% vs. 10% vs. 25% vs. 41%, respectively; P < 0.001) and death (1% vs. 0% vs. 3% vs. 9%, respectively; P < 0.001). Compared with class A, the 5-year hazard ratio for metastasis increased at 4.1 (B vs. A; P = 0.01), 10.1 (C vs. A; P < 0.001), and 30.0 (D vs. A; P < 0.001). The 5-year hazard ratio for death increased at 3.1 (C vs. A; P = 0.11) and 13.7 (D vs. A; P < 0.001) with no deaths in class B. CONCLUSIONS: Grouping of UM using TCGA classification predicts the risk of melanoma-related metastasis and death.

Hyperimmunoglobulin E syndrome: Genetics, immunopathogenesis, clinical findings, and treatment modalities.

The hyperimmunoglobulin E syndromes (HIESs) are very rare immunodeficiency syndromes with multisystem involvement, including immune system, skeleton, connective tissue, and dentition. HIES are characterized by the classic triad of high serum levels of immunoglobulin E (IgE), recurrent staphylococcal cold skin abscess, and recurrent pneumonia with pneumatocele formation. Most cases of HIES are sporadic although can be inherited as autosomal dominant and autosomal recessive traits. A fundamental immunologic defect in HIES is not clearly elucidated but abnormal neutrophil chemotaxis due to decreased production or secretion of interferon γ has main role in the immunopathogenesis of syndrome, also distorted Th1/Th2 cytokine profile toward a Th2 bias contributes to the impaired cellular immunity and a specific pattern of infection susceptibility as well as atopic-allergic constitution of syndrome. The ophthalmic manifestations of this disorder include conjunctivitis, keratitis, spontaneous corneal perforation, recurrent giant chalazia, extensive xanthelasma, tumors of the eyelid, strabismus, and bilateral keratoconus. The diagnosis of HIES is inconclusive, dependent on the evolution of a constellation of complex multisystemic symptoms and signs which develop over the years. Until time, no treatment modality is curative for basic defect in HIES, in terms of cytokines/chemokines derangement. Of note, bone marrow transplant and a monoclonal anti-IgE (omalizumab) are hoped to be successful treatment in future.

Femtosecond laser arcuate keratotomy for the correction of postkeratoplasty high astigmatism in keratoconus.

BACKGROUND: Astigmatism is the leading complication in visual recovery after penetrating keratoplasty (PKP) and deep anterior lamellar keratoplasty (DALK); in this study, we evaluated the outcome of femtosecond laser arcuate keratotomy (FLAK) after DALK and PKP in Iranian keratoconic patients. MATERIALS AND METHODS: In this prospective interventional case series, refractive and keratometric predictability, efficacy, and complications of FLAK for postkeratoplasty astigmatism in keratoconus were evaluated; 23 eyes of 23 consecutive patients (mean age of 32.43 ± 9.11 years) with high astigmatism were enrolled. The femtosecond laser performed paired 90°-angled arcuate incisions. RESULTS: Mean logarithm of the minimum angle of resolution of corrected and uncorrected visual acuity improved from preoperative values of 0.30 ± 0.18 and 0.85 ± 0.32 to 6-month values of 0.19 ± 0.17 and 0.65 ± 0.33, respectively (P < 0.05). Mean subjective astigmatism was 7.79 ± 2.64 diopter (D) preoperatively and 3.69 ± 2.25D at 6-month after surgery (P < 0.05). Surgically induced astigmatism was 9.27 ± 5.00D. Mean refractive spherical equivalent showed no significant (P = 0.69) hyperopic shift from - 4.21 ± 4.84D preoperatively to - 2.16 ± 6.09D postoperatively. Two (8.7%) microperforations were observed. CONCLUSION: FLAK is a relatively safe and effective method for the treatment of postkeratoplasty astigmatism.

Comparison of different doses of subconjunctival sunitinib with bevacizumab in the treatment of corneal neovascularization in experimental rats.

BACKGROUND: To compare the efficacy of subconjunctival administration of bevacizumab and different doses of sunitinib malate in reducing corneal neovascularization (CNV). MATERIALS AND METHODS: In this experimental study, central corneal cauterization was created in the right eye of fifty male Sprague-Dawley rats. On day 1 (1 week after cauterization), rats were randomly assigned into five treatment groups. Group control (n = 10) received subconjunctival injection of 0.02 ml of base saline solution. Group 1 (n = 10) received 0.02 ml of bevacizumab (25 mg/ml). Group 2, 3, and 4 (n = 10 for each group) were treated with 0.02 ml of sunitinib malate (10, 20, and 50 µg/ml, respectively). On days 1, 7, and 14, digital photographs of the cornea were taken, and the area of CNV was measured. RESULTS: During the 2-week follow-up, CNV area in treatment groups was less than in control group (P < 0.05). On day 7, corneal avascular area was highest in Group 3 at 63%. On day 14, the area of CNV in Groups 2 and 3 was less than in Group 1 (P = 0.031 and 0.011, respectively), but the difference between Groups 2 and 3 was not statistically significant (P = 0.552). The decreased CNV area on day 14 in Group 4 was significant in comparison to bevacizumab, but it was not significant on day 7 (P = 0.25 on day 7 and 0.002 on day 14). CONCLUSION: Subconjunctival sunitinib malate is more effective than bevacizumab in regressing CNV. This effect is more prominent on day 14.

Bupivacaine Injection for Management of Lagophthalmos Due to Long-Standing Idiopathic Facial Nerve Palsy.

PURPOSE: To report the results of bupivacaine injection into the orbicularis oculi muscle to treat lagophthalmos in patients with long-standing Bell palsy. METHODS: In this prospective interventional case series, bupivacaine, 5 ml of a 0.750% solution, was injected into the preseptal and pretarsal area of the orbicularis oculi in each of 10 patients with idiopathic peripheral facial nerve palsy. The measures of vertical eyelid apertures during open and closed eyes were made before the procedure and 1, 3, and 6 months after injection. RESULTS: A total of 10 eyes including 2 men and 8 women with an average age of 43 years (26-64 years) were studied. The mean amount of lagophthalmos before injection and after 6 months of follow up were 3.9 mm and 2.3 mm, respectively (p = 0.01)). The mean amount of corneal exposure before injection and after 6 months of follow up was 1.05 mm and 0.25 mm, respectively (p < 0.01). The mean scleral show in open eyes before injection and after 6 months of follow up were 1.20 mm and 0.75 mm, respectively (p = 0.08). The mean scleral show in closed eyes before injection and after 6 months of follow up were 1.95 mm and 1.15 mm, respectively (p = 0.01). All the patients reported significant decrease in epiphora. CONCLUSION: Bupivacaine injection in the paretic orbicularis oculi muscle improves eyelid closure and lagophthalmos and epiphora.

Malignant peripheral nerve sheath tumor of lacrimal nerve: a case report.

BACKGROUND: Orbital and periorbital presentation is rare for malignant peripheral nerve sheath tumors. These tumors are poorly defined spindle cell neoplasms of peripheral nerves and have not been reported to develop in the lacrimal gland to date. AIM: To report a rare presentation of malignant peripheral nerve sheath tumor in the orbital cavity. CASE REPORT: A 65-year-old man was admitted with the chief complaint of prominent right eye. His symptoms began 16 months prior to his admission. He had obvious limited ocular motion in upgaze and lateral gaze directions, as well as diplopia in all directions. He underwent imaging studies, and an iso-dense mass lesion in the lacrimal gland was revealed in orbital CT scan. In the MRI, there was a well-defined iso-intense mass lesion in T1-weighted images that was hyperintense in T2-weighted images and was enhanced with Gadolinium. Excisional biopsy revealed epithelioid and spindle cells with hyperchromatic rather than pleomorphic nuclei. Immunohistochemistry confirmed the presence of positive markers consistent with malignant peripheral nerve sheath tumor. CONCLUSION: Malignant peripheral nerve sheath tumor should be considered in the differential diagnosis of lacrimal gland tumors. Imaging studies may be helpful but tissue biopsy should be performed for accurate diagnosis. Complete excision of the mass lesion and adjunctive chemotherapy and radiotherapy should be considered in these cases.

Lower lid retraction in thyroid orbitopathy: lamellar shortening or proptosis?

To investigate any correlation between lower lid retraction and proptosis and also between lower lid retraction and lamellar length, as measured by fornix depth, in patients with thyroid eye disease (TED). One hundred and sixty-six eyes of 83 patients with TED were enrolled. The inferior fornix depth, Hertel exophthalmometry measurement, clinical activity score, and lower lid position were the main outcome variables. The correlation between lower lid position measurement and Hertel measurements and also between the lower lid position measurement and inferior fornix depth were evaluated using ANOVA and Pearson's tests. The mean age of subjects in patients with and without lid retraction was 42.8 ± 1.5 and 47.7 ± 1.6 years, respectively (P = 0.4). The inferior fornix depth in patients with and without lower lid retraction was 11.8 ± 1.5 and 11.8 ± 1.3 mm, respectively (P = 0.960). Pearson's analysis showed a significant correlation between the degree of proptosis and lower lid retraction in TED patients (P = 0.01). However, no significant correlation was found between the level of lower lid retraction and the fornix depth (P = 0.87). The main cause of lower lid retraction in TED is proptosis. The beneficial effect of orbital decompression on improvement of lower lid retraction must be considered during a stepwise surgical approach in TED patients.

Optical coherence tomography angiography in diabetic retinopathy: A major review.

Diabetic retinopathy (DR) is characterized by retinal vasculopathy and is a leading cause of visual impairment. Optical coherence tomography angiography (OCTA) is an innovative imaging technology that can detect various pathologies and quantifiable changes in retinal microvasculature. We briefly describe its functional principles and advantages over fluorescein angiography and perform a comprehensive review on its clinical applications in the screening or management of people with prediabetes, diabetes without clinical retinopathy (NDR), nonproliferative DR (NPDR), proliferative DR (PDR), and diabetic macular edema (DME). OCTA reveals early microvascular alterations in prediabetic and NDR eyes, which may coexist with sub-clinical neuroretinal dysfunction. Its applications in NPDR include measuring ischemia, detecting retinal neovascularization, and timing of early treatment through predicting the risk of retinopathy worsening or development of DME. In PDR, OCTA helps characterize the flow within neovascular complexes and evaluate their progression or regression in response to treatment. In eyes with DME, OCTA perfusion parameters may be of predictive value regarding the visual and anatomical gains associated with treatment. We further discussed the limitations of OCTA and the benefits of its incorporation into an updated DR severity scale.

Early Sign of Retinal Neovascularization Evolution in Diabetic Retinopathy: A Longitudinal OCT Angiography Study.

Purpose: To assess whether the combination of en face OCT and OCT angiography (OCTA) can capture observable, but subtle, structural changes that precede clinically evident retinal neovascularization (RNV) in eyes with diabetic retinopathy (DR). Design: Retrospective, longitudinal study. Participants: Patients with DR that had at least 2 visits. Methods: We obtained wide-field OCTA scans of 1 eye from each participant and generated en face OCT, en face OCTA, and cross-sectional OCTA. We identified eyes with RNV sprouts, defined as epiretinal hyperreflective materials on en face OCT with flow signals breaching the internal limiting membrane on the cross-sectional OCTA without recognizable RNV on en face OCTA and RNV fronds, defined as recognizable abnormal vascular structures on the en face OCTA. We examined the corresponding location from follow-up or previous visits for the presence or progression of the RNV. Main Outcome Measures: The characteristics and longitudinal observation of early signs of RNV. Results: From 71 eyes, we identified RNV in 20 eyes with the combination of OCT and OCTA, of which 13 (65%) were photographically graded as proliferative DR, 6 (30%) severe nonproliferative DR, and 1 (5%) moderate nonproliferative diabetic retinopathy. From these eyes, we identified 38 RNV sprouts and 26 RNV fronds at the baseline. Thirty-four RNVs (53%) originated from veins, 24 (38%) were from intraretinal microabnormalities, and 6 (9%) were from a nondilated capillary bed. At the final visit, 53 RNV sprouts and 30 RNV fronds were detected. Ten eyes (50%) showed progression, defined as having a new RNV lesion or the development of an RNV frond from an RNV sprout. Four (11%) RNV sprouts developed into RNV fronds with a mean interval of 7.0 months. Nineteen new RNV sprouts developed during the follow-up, whereas no new RNV frond was observed outside an identified RNV sprout. The eyes with progression were of younger age (P = 0.014) and tended to be treatment naive (P = 0.07) compared with eyes without progression. Conclusions: Longitudinal observation demonstrated that a combination of en face OCT and cross-sectional OCTA can identify an earlier form of RNV before it can be recognized on en face OCTA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Retinal ischemic cascade: New insights into the pathophysiology and imaging findings.

Retinal ischemia gives rise to a complex spectrum in which the cumulative profile of ischemia of the middle and inner retina can be highly variable. We reviewed the current knowledge on paracentral acute middle maculopathy (PAMM) pathophysiology and accompanying risk factors, the middle and inner retinal vasculature and blood flow, and the vulnerability of the middle retina in vaso-occlusive disorders. The inner nuclear layer (INL) is easily affected by slight degrees of retinal hypoperfusion and ischemia. INL infarction starts at perivenular sites, manifesting as skip PAMM lesions and a fern-like appearance in cross-sectional and en face views, respectively. With horizontal progression, INL infarction may develop into diffuse globular PAMM. If vertical progression occurs, the entire middle and inner portions of the retina can be affected. Transmural infarction of the middle and inner retina would be at the end of this spectrum. This gradient of ischemic progression resembles an ischemic cascade. We review the evidence supporting the term "retinal ischemic cascade," which encompasses a broad continuum of manifestations with roots in middle retinal infarction. With this terminology, variations in spatial and temporal progression and resolution of ischemia can also be delivered; it further enables addressing the possible associations between the middle and inner retinal ischemic patterns.

Inverted ILM Flap Technique in Optic Disc Pit Maculopathy.

Purpose: To present the outcome of optic disc pit maculopathy (ODPM) managed successfully with an inverted internal limiting membrane (ILM) flap over the optic disc. A narrative review of ODPM pathogenesis and surgical management techniques are also provided. Case Report: This prospective interventional case series included three eyes of three adult patients (25-39 years old) with unilateral ODPM and a mean duration of unilaterally decreased visual acuity of 7.33 ± 2.40 months (4-12 months). The pars plana vitrectomy with posterior vitreous detachment induction was performed on eyes, followed by an inverted ILM flap insertion over the optic disc and gas tamponade. Patients were followed for 7-16 weeks postoperatively; best-corrected visual acuity (BCVA) improved dramatically in one patient from 2/200 to 20/25. BCVA in other patients improved two and three lines - to 20/50 and 20/30, respectively. A significant anatomical improvement was achieved in all three eyes, and no complication was detected throughout the follow-up period. Conclusion: Vitrectomy with inverted ILM flap insertion over the optic disc is safe and can yield favorable anatomical improvement in patients with ODPM.

Erratum: Inverted ILM Flap Technique in Optic Disc Pit Maculopathy.

[This corrects the article DOI: 10.18502/jovr.v18i2.13189.].

Utility of En Face OCT for the Detection of Clinically Unsuspected Retinal Neovascularization in Patients with Diabetic Retinopathy.

PURPOSE: To assess the value of en face OCT for detecting clinically unsuspected retinal neovascularization (RNV) in patients with nonproliferative diabetic retinopathy (NPDR). DESIGN: A retrospective, cross-sectional study. PARTICIPANTS: Treatment-naïve patients clinically graded as NPDR in an ongoing prospective observational OCT angiography (OCTA) study at a tertiary care center. METHODS: Each patient underwent imaging of 1 eye with a spectral-domain OCTA, generating a 17 × 17-mm widefield image by montaging four 9 × 9-mm scans. Two independent graders examined a combination of en face OCT, en face OCTA with a custom vitreoretinal interface slab, and cross-sectional OCTA to determine the presence of RNV. We measured the area of RNV flow within RNV lesions on en face OCTA. MAIN OUTCOME MEASURES: Detection rate of clinically occult RNV with OCT and OCTA. RESULTS: Of 63 enrolled eyes, 27 (43%) were clinically graded as severe NPDR, 16 (25%) as moderate NPDR, and 20 (32%) as mild NPDR. Using the combination of en face OCT, en face OCTA, and cross-sectional OCTA, the graders detected 42 RNV lesions in 12 (19%) eyes, of which 8 (67%) were graded as severe NPDR, 2 (17%) as moderate NPDR, and 2 (17%) as mild NPDR. The sensitivity of en face OCT alone for detecting eyes with RNV was similar to that of en face OCTA alone (100% vs. 92%; P = 0.32), whereas the specificity of en face OCT alone was significantly lower than that of en face OCTA alone (32% vs. 73%; P < 0.001). For detecting individual RNV lesions, the en face OCT was 100% sensitive, compared with 67% sensitivity for the en face OCTA (P < 0.001). The area of RNV lesions that manual grading with en face OCTA alone missed was significantly smaller than that of manually detectable RNV (Mean [standard deviation] RNV flow area, 0.015 [0.020] mm2 vs. 0.16 [0.36] mm2; P < 0.001). CONCLUSION: The combination of en face OCT and OCTA can detect clinically occult RNV with high sensitivity. For screening these small lesions, en face OCT may be a useful imaging modality. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Color Doppler ultrasound for evaluation of vasomotor activity in patients with carpal tunnel syndrome.

BACKGROUND: Patients with carpal tunnel syndrome (CTS) have a variety of vasomotor symptoms. Here, we aimed to study the vasomotor activity of the radialis indicis (RI) artery (median nerve territory) and the radial palmar digital (RPD) artery of the little finger (ulnar nerve territory) before and after sympathetic stimulation in CTS patients using color Doppler ultrasound. METHODS: We performed a cross-sectional study of 46 consecutive CTS patients plus 36 healthy controls. All patients underwent electromyography studies and were classified into mild and moderate/severe groups according to electrodiagnostic findings. Color Doppler examination of the RI artery and the RPD artery of the little finger were performed with the participants in a relaxed sitting position and after a deep breath followed by a cough (sympathetic stimulation). The pulsatility index (PI) was recorded at the point of maximal change in waveform, before and after this stimulus. RESULTS: The PI of RI artery was significantly lower (p < 0.01) in CTS patients than healthy controls, both before and after stimulation. The changes in PI of RI artery after stimulation were significantly lower in CTS patients than healthy controls (1.18 ± 0.37 vs. 5.41 ± 0.87; p < 0.001). The same pattern was seen for PI of RI artery when comparing patients with mild vs. moderate/severe CTS. No difference was found in PI of RPD artery of the 5th finger between patients vs. controls and between patients with mild vs. moderate/severe CTS, both before and after stimulation. CONCLUSIONS: We showed that color Doppler ultrasound can readily determine impaired vasomotor activity in CTS patients.