Cycle threshold values of SARS-CoV-2 RNA in conjunctival swabs and nasopharyngeal secretions: a comparative study from a tertiary care center in India.

PURPOSE: To detect the viral RNA load of SARS-CoV-2 in conjunctival swabs of COVID-19 patients, and compare with nasopharyngeal swabs. METHODS: Conjunctival swabs of COVID-19 patients (with PCR positive nasopharyngeal swabs) were subjected to quantitative reverse transcription-polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2 RNA. The cycle threshold (Ct) values of Open Reading Frame 1 (ORF 1 Ab gene) and nucleoprotein (N gene) PCRs were used to assess the viral RNA load, and compare them with the baseline values of nasopharyngeal swabs. RESULTS: Of 93 patients, 17 (18.27%) demonstrated SARS-CoV-2 RNA in conjunctival swabs. Baseline nasopharyngeal swabs were collected at a median of 2 days; while, the conjunctival swabs were collected at median 7 days, from onset of illness (p < 0.001). Despite a significant delay in conjunctival swab collection than nasopharyngeal swabs, the Ct values (ORF or N gene PCRs) were comparable between nasopharyngeal swab and conjunctival swab samples. Subsequently, during the recovery period, in four of these 17 patients (with conjunctival swab positivity), when the second nasopharyngeal swab was 'negative', the conjunctival swab was 'positive'. CONCLUSION: The conjunctival swabs demonstrated SARS-CoV-2 RNA in 17 (18.27%) of 93 COVID-19 patients. Our results may suggest a delayed or a prolonged shedding of the virus/viral RNA on the ocular surface than in nasopharyngeal mucosa.

MULTICOLOR CONFOCAL SCANNING LASER OPHTHALMOSCOPE IMAGING IN POSTERIOR UVEITIS.

PURPOSE: To study the utility of MultiColor confocal scanning laser ophthalmoscope imaging (MCI) in identifying the morphology of uveitic lesions compared with conventional color fundus photography (CFP) in patients with posterior uveitis. METHODS: In this prospective observational study, subjects with posterior uveitis underwent MCI and CFP. The images obtained by the two modalities were analyzed by two independent reviewers for vitreoretinal surface abnormalities, retinal fluid and hemorrhages, and depth/location of lesions. These findings were compared with the clinical findings and other imaging techniques. RESULTS: Sixty-nine eyes of 43 patients (25 men) with mean age of 33.5 ± 13.9 years were studied. MultiColor imaging had better sensitivity and specificity in detecting vitreoretinal interface abnormalities, such as epiretinal membrane and inner retinal striae, compared with CFP. MultiColor imaging failed to detect retinochoroiditis lesions in 5 of 6 eyes (83%) and choroiditis in 9 46 eyes (20%), which were detected on CFP and clinical examination. Also, MCI showed a high false-positive rate of 34% in detecting intraretinal hemorrhages. CONCLUSION: Retinochoroidal lesions in posterior uveitis may be poorly identified on MCI compared with CFP and clinical examination. One must exercise caution in commenting on disease morphology based on MCI alone.

LONGITUDINAL FOLLOW-UP OF TUBERCULAR SERPIGINOUS-LIKE CHOROIDITIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To analyze and describe serial follow-up of choriocapillaris alterations in tubercular serpiginouslike choroiditis (SLC) using optical coherence tomography angiography (OCTA) and to compare it with multimodal imaging. METHODS: In this prospective cohort study, patients with active tubercular SLC underwent OCTA using Optovue RTVue XR Avanti and other imaging techniques including enhanced-depth imaging OCT (EDI-OCT) (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Serial imaging was performed for a total follow-up of 3 months. Choriocapillaris alterations at the site of lesions were analyzed on OCTA imaging, and their mean lesion areas were calculated. RESULTS: Twenty-six eyes (26 patients; 20 males; mean age: 32.68 ± 10.56 years) were included. Fourteen eyes had active multifocal lesions (n = 39), whereas 12 eyes had active placoid lesions (n = 12). At baseline, OCTA showed hyporeflective flow deficit lesions corresponding to the hypofluorescent lesions on indocyanine green angiography in all eyes. In the multifocal type of SLC, the mean lesion area decreased in all eyes compared with baseline, and lesions with a lesion area less than 0.1 mm2 on OCTA showed near-complete resolution with minimal choriocapillaris atrophy. In comparison, all eyes with a placoid type of SLC showed no significant reduction in the lesion area and showed extensive choriocapillaris atrophy. CONCLUSION: Optical coherence tomography angiography has the unique ability to demonstrate pathological flow impairment at the level of choriocapillaris in active tubercular SLC. Serial OCTA analysis reveals that large tubercular SLC lesions result in choriocapillaris atrophy as the lesions heal, whereas smaller multifocal lesions show resolution of choriocapillaris hypoperfusion with minimal atrophy.

BACILLARY LAYER DETACHMENT IN ACUTE VOGT-KOYANAGI-HARADA DISEASE: A Novel Swept-Source Optical Coherence Tomography Analysis.

PURPOSE: To report the frequency, optical coherence tomography (OCT) findings, and visual and anatomic outcomes of patients with acute Vogt-Koyanagi-Harada disease presenting with the bacillary layer detachment (BLD) (intraretinal split at the photoreceptor inner segment myoid). METHODS: This was a retrospective analysis of a consecutive series of patients with Vogt-Koyanagi-Harada disease having a minimum follow-up of 6 months. All patients had swept-source OCT, fluorescein angiography, and indocyanine green angiography performed at baseline. The characteristics of serial swept-source OCT were recorded and analyzed. RESULTS: Sixty-two subjects (42 women; age: 34.2 ± 12 years) with Vogt-Koyanagi-Harada disease were included. 118 eyes (95.2%) had serous retinal detachment at presentation. 112 eyes (94.9%) showed the BLD at baseline. In 8 of 112 (7.1%) eyes with the BLD, the external limiting membrane at the anterior aspect of the BLD showed focal discontinuity. The interdigitation zone at the base of the BLD showed discontinuity in 53 of 112 (47.3%) eyes with the BLD. The ellipsoid zone could not be identified as a separate hyperreflective line at the base of the BLD in 102 of 112 eyes (91.1%). Bacillary layer detachments resolved within 3.4 ± 1.3 days after intravenous methylprednisolone therapy with improvement in the best-corrected visual acuity from 0.96 to 0.4 logarithm of the minimum angle of resolution (20/184 Snellen's equivalent) (P < 0.001). Resolution of serous retinal detachment was observed after 5.9 ± 2.6 days. CONCLUSION: In eyes with acute Vogt-Koyanagi-Harada disease, the BLD is a common finding and represents a split in the photoreceptor layer at the inner segment myoid and can be differentiated from serous retinal detachment using swept-source OCT. In addition, resolution of the BLD and photoreceptor recovery can be evaluated using serial swept-source OCT.

Mycobacterium tuberculosis does not show evidence of molecular DNA in human cadaveric ocular tissues in an endemic setting.

BACKGROUND: Mycobacterium tuberculosis (MTB) in latent infection has been demonstrated in pulmonary/extra-pulmonary locations (lung, spleen, liver, kidney, adipose tissue) in autopsy studies, but its presence in ocular tissues in the latent state is not known. METHODS: We conducted molecular and histopathological study of 100 cadaver eyes (50 humans) who died from causes other than tuberculosis (TB) (and were potential candidates for corneal transplantation) to detect MTB in ocular tissues in an endemic setting. After removal of the corneal button, an 8 to 10 mm block of tissue (choroid, retina and part of the vitreous) was excised from the remaining globe for DNA isolation. Gel-based IS6110 and devR3 polymerase chain reaction (PCR) assays were done, followed by real-time PCR using beta actin gene as an internal control. Sixteen randomly selected DNA samples were double checked using a commercial kit for MTB and non-tuberculous mycobacteria (NTM) DNA. The remaining larger part of the globe was subjected to histopathology. RESULTS: The mean age was 65.14 ± 18 years. All 100 samples were negative for both IS6110 and devR, and all 16 samples were negative with NTM MTB commercial kit. All samples were negative with Ziehl-Neelsen stain for acid fast bacilli and none showed any inflammation or granulomatous pathology. CONCLUSIONS: MTB could not be detected in human ocular tissues in latent state in India, a TB-endemic country. This may suggest the inability of MTB to seed ocular tissues in the latent state, unlike other organs which serve as reservoirs for the bacilli in the absence of manifest disease.

OUTCOME OF ENDOVASCULAR PROCEDURES ON OCULAR FINDINGS IN TAKAYASU ARTERITIS.

PURPOSE: To evaluate the outcome of endovascular procedures on ocular findings in patients with Takayasu arteritis. METHODS: Retrospective study of patients who underwent percutaneous endovascular stenting of aortic arch arteries for Takayasu arteritis (TA) and who had documented retinopathy findings before and after the procedure. Change in visual acuity, regression of retinopathy, and development of complications after endovascular procedure were studied over a follow-up of 6 months. RESULTS: Ten eyes of five patients were included. Eyes which had Stage II or less of retinopathy before the endovascular procedure had favorable outcome; however, those with advanced stage of retinopathy at presentation had poor outcomes. Patients who underwent revascularization of both-sided arteries within 1 month had better anatomical and functional outcomes as compared with those who underwent sequential endovascular procedures on their arteries after a gap of 3 months or more. CONCLUSION: Percutaneous endovascular stenting of aortic arch arteries, affected in TA, can lead to reversal of retinopathy changes and restoration of vision if done before neovascular complications set in.

FRACTAL DIMENSION AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF THE CENTRAL MACULA AFTER REPAIR OF RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: Patients with macula-off rhegmatogenous retinal detachments (RRDs) may have suboptimal visual recovery, despite successful reattachment due to various reasons. This study was performed to evaluate the retinal microvasculature in subjects undergoing surgery for RRD using optical coherence tomography angiography. METHODS: In this case-control study, the analysis of optical coherence tomography angiography findings of 19 eyes of 19 patients (15 men) who underwent RRD surgery at a tertiary institute were compared with 19 eyes of 19 age- and sex-matched healthy subjects with no known ocular disease. 3 × 3-mm optical coherence tomography angiography scans were obtained at 3 months postoperatively and analyzed. Optical coherence tomography angiography images of patients with RRD and control subjects were analyzed for capillary density index and fractal dimensions. RESULTS: Mean age of the patients was 40.21 years, and the mean age of controls was 43.73 years. Eight eyes underwent scleral buckling alone, and 11 eyes underwent primary vitrectomy with gas tamponade (C3F8 gas) for macula-off RRD. None of the eyes had redetachment during the follow-up at 3 months. Mean capillary density index among patients was 33.28% ± 0.99% and 34.06% ± 2.22% in the superficial and deep retinal plexuses, respectively, compared with 36.11% ± 1.29% and 37.52% ± 1.24% among controls (P < 0.001). The mean fractal dimension was lower among subjects compared with controls (1.46 vs. 1.61 in the superficial plexus, P < 0.001; 1.58 vs. 1.64 in the deep plexus, P < 0.001). CONCLUSION: Optical coherence tomography angiography demonstrates significant reduction in mean capillary density index and fractal dimension in patients after surgery for RRD in our patients. Thus, reduction in vascular perfusion and branching pattern identified using novel analysis techniques on optical coherence tomography angiography images may provide an insight into the reasons for suboptimal visual gain after RRD surgery.

Immune Profiling of T Cells Infiltrating Vitreous Humor in Tubercular Uveitis.

PURPOSE: To assess cellular composition and local cytokine response in vitreous humor of tubercular uveitis. METHODS: Cells were collected from vitreous cassettes and peripheral blood of 8 tubercular uveitis and 5 control subjects, undergoing vitrectomy and analyzed by flow cytometry for cellular composition, activation status, proinflammatory cytokine expression, and uptake of TLR9 ligand, CpG ODN 2216. RESULTS: CD3 + T cells with equal proportion of CD4+ and CD8 + T cells formed major fraction of infiltrating cells. The vitreous humor showed higher expression of recent activation marker, CD69, and proinflammatory cytokines, IFN-γ and IL-17A, in CD4 + T cells as compared to peripheral blood. Lastly, intraocular CD4 + T cells showed reduced uptake of ODN 2216 than peripheral blood. CONCLUSIONS: Our results indicate that local antigenic stimuli trigger T cell infiltration and activation of CD4 + T cells that are hyporesponsive to TLR9 stimulation. These infiltrating T cells might be responsible in further aggravating ocular inflammation.

OCT angiography demonstrates retinal angiomatous proliferation and chorioretinal anastomosis of type 3 neovascularization.

PURPOSE: To report the OCT angiography findings of type 3 neovascularization. METHODS: Two cases (one each with retinal angiomatous proliferation and chorioretinal anastomosis) are reported, in which the conventional fundus fluorescein angiography and spectral-domain optical coherence tomography findings were inconclusive. RESULTS: OCT angiography demonstrated flow within the abnormal anastomotic network and delineated the extent of the lesion with respect to the retinal layers. CONCLUSION: OCT angiography enables a quick diagnosis of type 3 neovascularization by demonstrating a supranormal flow within the lesion and delineates the lesion within different retinal layers.

Clinical and Neuro-ophthalmologic Predictors of Visual Outcome in Idiopathic Intracranial Hypertension.

Despite the potential of Idiopathic Intracranial Hypertension (IIH) to cause visual morbidity, limited literature is available focussing on predictors of visual outcome in IIH. This study was planned to assess visual morbidity in patients of IIH in terms of clinical and neuro-ophthalmo- logical parameters. In this prospective study of 40 patients of IIH, neuro-ophthalmological parameters were noted in the form of visual acuity, visual field, contrast sensitivity, Retinal Nerve Fibre Layer thickness, and visual evoked potential. Visual outcome was defined in using specific criteria. Final visual outcome of patients was compared with clinical and neuro-ophthalmologic para- meters to determine any correlation. The most common presenting clinical symptoms were headache (85%) and Transient visual obscurations (TVOs) (52.5%). In univariate analysis severity of visual loss, Cerebro Spinal Fluid (CSF) pressures and abnormal Visual evoked potential (VEP) were associated with worse visual outcome or need of aggressive management. When adjusted for severity of visual loss no independent clinical/neuroophthalmic predictor could be established. High CSF opening pressure, worsening vision/papilledema, greater Retinal Nerve Fiber Layer (RNFL) thickness and abnormal VEPs may be some of the alarming signs for physicians, but none of these parameters can be used as an independent predictor for visual outcome in isolation. Visual loss at presentation is probably the most important predictor of the final visual outcome in these patients. This may also suggest that patients presenting in an advanced disease course (with worse visual status) fair badly despite best medical/surgical management. Early diagnosis and prompt management is the cornerstone of management.

Transplantation of lineage-negative stem cells in pterygopalatine artery ligation induced retinal ischemia-reperfusion injury in mice.

Retinal ischemia is a condition associated with retinal degenerative diseases such as glaucoma, diabetic retinopathy, and other optic neuropathies, leading to visual impairment and blindness worldwide. Currently, there is no therapy available for ischemic retinopathies. Therefore, the aim of this study was to test a murine model of pterygopalatine artery ligation-induced retinal injury for transplantation of mouse bone marrow-derived lineage-negative (lin-ve) stem cells. The mouse external carotid artery and pterygopalatine artery were ligated for 3.5 h followed by reperfusion. The model was validated through fundus fluorescein angiography, laser Doppler and FITC dextran perfusion in whole-mounts. Lin-ve stem cells isolated from mouse bone marrow were transplanted through tail-vein, which showed migration to retina leading to decrease in GFAP expression. The neurotrophic factors such as BDNF and FGF2 showed enhanced expression in the retina. The functional analysis with electroretinogram did not demonstrate any significant changes before or after injury or stem cell transplantation. This study shows a neuroprotective potential in lin-ve stem cells in the retinal ischemia induced by pterygopalatine artery ligation and presents a practical model for validating therapies for ischemic disorders of the retina in future.

Morphological differences between optic disc collaterals and neovascularization on optical coherence tomography angiography.

BACKGROUND: To study morphological features of optic disc venous collaterals (OVCs) and neovascularization of optic disc (NVD) on optical coherence tomography angiography (OCTA). METHODS: Patients with OVCs and NVDs secondary to ischemic retinal diseases were prospectively enrolled. Multimodal imaging was performed using color fundus photography, fluorescein angiography (FA), and OCTA. Morphological evaluation of en-face structural OCT, cross-sectional and en-face OCTA was performed. RESULTS: Twenty eyes (20 patients; OVCs: n = 10 and NVD: n = 10) were included. OVCs appeared as small, loopy vessels distinct from surrounding peripapillary capillaries on OCTA in the radial peripapillary capillary frame. NVDs appeared as a mesh of fine caliber, raised vessels best seen in the vitreous slab of OCTA. Flow signals in these vascular alterations correlated well with hyperfluorescence on FA. CONCLUSIONS: OCTA provides improved visualization of NVDs and OVCs in ischemic retinal diseases such as diabetic retinopathy and retinal vein occlusions compared to conventional FA.

NOVEL FINDINGS ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH TUBERCULAR SERPIGINOUS-LIKE CHOROIDITIS.

PURPOSE: To analyze and describe the imaging characteristics of tubercular serpiginous-like choroiditis using optical coherence tomography angiography (OCTA) and to compare these findings with multimodal imaging. METHODS: In this prospective cross-sectional study, multimodal imaging was performed in subjects with tubercular serpiginous-like choroiditis using OCTA (Optovue RTVue XR Avanti), enhanced-depth imaging OCT (Heidelberg Spectralis), fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Distinct morphologic features of the retinochoroidal vasculature at the sites of choroiditis lesions were analyzed on OCTA imaging. Multimodal imaging analysis was performed to study the changes observed on OCTA. RESULTS: Eighteen eyes (18 subjects, 16 males) were included in the study. The en face OCTA images demonstrated discrete areas of flow void beneath the retinal pigment epithelium-Bruch membrane layer suggestive of choriocapillaris hypoperfusion that corresponded well with indocyanine green angiography, especially in the chronic phase. Additional information such as areas of preserved choriocapillaris, vascular tufts, and tangled vessels were observed using OCTA among lesions in advanced stages of healing. Compared with indocyanine green angiography, the areas of choriocapillaris atrophy appeared better defined on OCTA and correlated well with enhanced-depth imaging OCT. CONCLUSION: The OCTA images provide high-resolution structural information of the retinochoroidal vasculature in tubercular serpiginous-like choroiditis. Morphologic information obtained from OCTA images correlates well with and supplements other imaging techniques such as indocyanine green angiography and enhanced-depth imaging OCT.

Chronic Invasive Fungal Sinusitis Presenting as Inferior Altitudinal Visual Field Defect.

A young male with acute blurring of vision (6/9) complained of an inferior altitudinal field defect in right eye. Clinical ophthalmological examination was normal. Magnetic resonance imaging (MRI) of the brain revealed the expansion and mucosal thickening of right posterior ethmoid and sphenoid sinuses and opacified right maxillary sinus. Surgical intervention (transethmoidal sphenoidotomy) and histopathological examination revealed chronic invasive granulomatous fungal sinusitis. Anti-fungal therapy led to resolution of visual complaints and restoration of visual field defects.

Visual outcome in 2000 eyes following microscopic transsphenoidal surgery for pituitary adenomas: Protracted blindness should not be a deterrent.

OBJECTIVE: To study the visual outcome after surgery for pituitary adenomas with visual deficits. MATERIALS AND METHODS: All patients with pituitary adenoma, who presented from 2003-2014 in a tertiary care institute, were included in the study. Surgical outcome was measured in terms of difference in visual acuity, visual fields and optic fundus parameters documented before surgery, immediate post-operatively and at the third, and twelfth months following surgery. RESULTS: At the initial presentation, visual involvement was seen in 87.2% patients. One year after surgery, 93.2% patients having abnormal vision had improvement in visual acuity and visual fields; whereas visual parameters were static in 5.2%. Visual deterioration occurred only in 1.3% patients. Moreover, five-percent of those who did not even have perception of light at presentation experienced significant improvement in vision after surgery. The shorter the duration of visual symptoms, the more was the percentage of patients having faster recovery in the early postoperative period. CONCLUSION: Post-operative visual outcome was directly proportional to the pre-operative visual acuity. Though the visual outcome was good in the long run irrespective of the duration of symptoms, the speed of recovery was proportional to the duration of visual deficits. However, presence of long-standing visual symptoms should not deter us to subject the patient to surgery. Even patients who are completely visually impaired for years should be subjected to surgery as early as feasible.

Detection of Mycobacterium tuberculosis genome in vitreous fluid of eyes with multifocal serpiginoid choroiditis.

PURPOSE: To compare 3 different molecular techniques to detect the Mycobacterium tuberculosis genome in vitreous fluid of eyes with multifocal serpiginoid choroiditis (MSC). DESIGN: Prospective, interventional case series. PARTICIPANTS: Eleven patients (11 eyes) with active MSC in at least 1 eye underwent diagnostic pars plana vitrectomy (PPV) between October 2012 and December 2013. METHODS: Vitreous fluid samples were subjected to multitargeted polymerase chain reaction (PCR) for a M. tuberculosis assay, the Gene Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA), and a line probe assay (GenoType MTBDRplus; Hain Lifescience, GmbH, Nehren, Germany). The samples with positive results were subjected to rpoB gene sequencing to demonstrate rifampicin resistance. The clinical details, digital fundus imaging, and treatment details and outcomes also were noted. MAIN OUTCOME MEASURES: Detection of the M. tuberculosis genome and rifampicin resistance in the vitreous samples. RESULTS: Of the 11 eyes subjected to PPV, the multitargeted PCR results for tuberculosis were positive for 10 eyes, the MTBDRplus assay results were positive in 6 eyes, and the Gene Xpert MTB/RIF assay results were positive in 4 eyes. Rifampicin resistance was detected in 3 eyes by rpoB gene sequencing, in 3 eyes by the MTBDRplus assay, and in 1 eye by the Gene Xpert MTB/RIF assay. CONCLUSIONS: We detected the M. tuberculosis genome in the vitreous fluid of eyes with MSC using 3 different molecular techniques. Rifampicin resistance was detected for the first time in eyes with MSC.

Extra-Pituitary Birth Defects May Predict Diagnosis of Congenital Hypopituitarism in a Short Child.

BACKGROUND: Extra-pituitary birth defect (EPBD) in children with congenital hypopituitarism is largely unknown. OBJECTIVE: The study aims to evaluate the incidence and pattern of EPBD in children with congenital hypopituitarism and to evaluate whether it can serve as a clue to diagnose this condition. PATIENTS AND METHODS: Retrospective analysis of hospital record of patients of short stature due to various etiology from which patients with congenital hypopituitarism with age ≥18 years were recruited for the analysis. Clinical, hormonal, radiological and ocular electrophysiological studies were done in all patients and all EPBD were noted. RESULTS: Twenty seven patients (79%) had multiple pituitary hormone deficiency (MPHD) of which growth hormone was universal followed by gonadotropin (62%), TSH (59%), ACTH (44%) and prolactin (12%). Nineteen patients (56%) had multiple EPBD in various combinations. Twenty three ocular abnormalities were present in 12 patients (35%). Nine patients (26%) had other associated EPBD along with ocular abnormalities while 3 had ocular abnormalities without any other associated birth defect. Skeletal defects were present in 10 patients (29.5%). On the contrary, 5 patients in the EPBD group had total 15 visual defects. The most common abnormality of the visual system were abnormal visual evoke response (VER, 18%), followed by strabismus (15%), visual acuity (VA, 12%), electroretinogram (ERG) and electrooculogram (EOG) 8% each and visual field defect 6%. There was a trend towards early age at presentation with EPBD. CONCLUSIONS: Presence of EPBD in a short child is a sensitive marker to diagnose congenital hypopituitarism. Subtle abnormalities of visual pathway without absent septum pellucidum or midline brain defects were common.