Proteomic profile of vitreous in patients with tubercular uveitis.

OBJECTIVE: To elucidate disease-specific host protein profile in vitreous fluid of patients with intraocular inflammation due to tubercular uveitis (TBU). METHODS: Vitreous samples from 13 patients with TBU (group A), 7 with non-TBU (group B) and 9 with no uveitis (group C) were analysed by shotgun proteomics using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were subjected to pathway analysis using WEB-based Gene SeT Analysis Toolkit software. RESULTS: Compared to control groups (B + C combined), group A (TBU) displayed 32 (11 upregulated, 21 downregulated) DEPs, which revealed an upregulation of coagulation cascades, complement and classic pathways, and downregulation of metabolism of carbohydrates, gluconeogenesis, glucose metabolism and glycolysis/gluconeogenesis pathways. When compared to group B (non-TBU) alone, TBU displayed 58 DEPs (21 upregulated, 37 downregulated), with an upregulation of apoptosis, KRAS signaling, diabetes pathways, classic pathways, and downregulation of MTORC1 signaling, glycolysis/gluconeogenesis, and glucose metabolism. CONCLUSION: This differential protein profile provides novel insights into the molecular mechanisms of TBU and a baseline to explore vitreous biomarkers to differentiate TBU from non-TBU, warranting future studies to identify and validate them as a diagnostic tool in TBU. The enriched pathways generate interesting hypotheses and drive further research.

Role of CT Chest and Cytology in Differentiating Tuberculosis from Presumed Sarcoidosis in Uveitis.

Purpose: To report the role of CT chest and cytology in suspected tubercular and sarcoid uveitis. Methods: This is a retrospective, interventional case series of 376 uveitis patients with suspected ocular tuberculosis (TB)/sarcoidosis seen between January 2010 and April 2015 at the Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh. All underwent CT chest, and had following inclusion criteria: (1) Presence of active granulomatous anterior/intermediate/posterior uveitis or panuveitis; (2) a documented tuberculin skin test/QuantiFERON-TB Gold test; (3) all other causes of infectious/non-infectious uveitis ruled out. A total of 206 patients had abnormal CT chest, of which 147 patients with minimum four months follow up were studied. Based on CT findings and amenability of involved lymph nodes, conventional transbronchial needle aspiration (TBNA)/endobronchial ultrasoundguided TBNA (EBUS-TBNA) or fine needle aspiration cytology (FNAC) of peripheral nodes was performed by an interventional pulmonologist. All smears were subjected to cytopathological examination, and Ziehl-Neelsen staining for acid-fast bacilli (AFB). The detection of the underlying etiology (TB or sarcoidosis) was the main outcome measure. Results: CT chest demonstrated mediastinal/hilar lymph nodes in 123/147 (83.7%) patients. Twenty four (16.2%) patients with parenchymal involvement were diagnosed TB (n = 20) or sarcoidosis (n = 4). Sixty nine patients with subcentimetric lymph nodes that were not amenable to biopsy were diagnosed clinico-radiologically as TB (42) and sarcoidosis (27). Fifty-four patients underwent biopsy from various sites that diagnosed TB and sarcoidosis in 21 (38.2%) patients each. Five TBLB/EBUS TBNA smears and seven FNAC smears demonstrated AFB. Conclusions: In systemically asymptomatic individuals presenting with uveitis, CT chest helped to establish the diagnosis of TB/sarcoidosis in 71.43% cases (105 out of 147) using only the clinico-radiological criteria, while a confirmed diagnosis of TB/sarcoidosis was possible only in 42 cases (28.57%) by EBUS/TBNA guided cytological examination.

Utility of MALDI-TOF mass spectrometry in an outbreak investigation of acute endophthalmitis following intravitreal injection.

Bevacizumab, a recombinant humanized monoclonal antibody to inhibit tumour angiogenesis, is available for off-label use for treating choroidal neovascularization. Outbreaks have been reported after use of this drug, either because of contamination during manufacturing or the practice of multiple doses being administered from a single vial to different patients. In our institute we investigated one endophthalmitis outbreak following intravitreal injection of bevacizumab, rapidly identified the Stenotrophomonas maltophilia as the causative agent, and established the contaminated bevacizumab vial as the source using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF-MS) typing. The study emphasizes the need for early diagnosis of the source and pathogen for appropriate control measures.

Survival and morbidity among two cohorts of extremely low birth weight neonates from a tertiary hospital in northern India.

This study was conducted to compare the survival and morbidity of extremely low birth weight neonates born during two different time periods (2009-10 and 2001-02) at a Level III referral neonatal unit in Northern India. All consecutive intramural extremely low birth weight neonates (<1000g), irrespective of gestation, and admitted to Intensive Care were enrolled. 149 and 123 neonates were enrolled during 2009-10 and 2001-02, respectively. The baseline characteristics were comparable except for mean birth weight, which was lower during 2009-10 (843±108g vs 885±126g, P=0.003). Surfactant therapy (54% vs 18%, P<0.001), non-invasive ventilation (28% vs 6%, P<0.001), high frequency ventilation (24% vs 4%, P=0.001), IVH (52% vs 25%, P<0.001) and PDA (34% vs 18%, P=0.004) were significantly more during 2009-10. Culture positive sepsis (33% vs 51%, P=0.003) and ROP rates (7% vs 23%, P=0.042) were significantly higher during 2001-02. Overall survival was similar; however, neonates between 28-30 weeks gestation had better survival (63%) during 2009-10 compared to 2001-02 (38%), P=0.009. Survival in neonates 28-30 weeks improved during this period while overall survival remained the same.

Dark spot in fibrinous central serous chorioretinopathy masquerading choroiditis.

PURPOSE: The authors observed that eyes with acute fibrinous central serous chorioretinopathy (CSC) masquerading active choroiditis had a "dark spot" within the yellow fibrinous deposit. The present study aims to describe this sign as a clinical indicator of acute serofibrinous exudative detachment, thus helping to differentiate it from active choroiditis. METHOD: The authors retrospectively reviewed the records of 19 patients of fibrinous CSC masquerading active choroiditis. Color fundus photographs, fundus fluorescein angiogram (FFA), and optical coherence tomography (OCT) at baseline and follow-up were studied for a dark spot. The systemic steroids were stopped and all patients were followed up. RESULTS: There were 12 men and 7 women with a mean age of 39.8 years. Fourteen patients had received systemic steroids. Funduscopy revealed creamy yellow subretinal lesion/s simulating active choroiditis lesion in all eyes and exudative retinal detachment in 9 eyes. The dark spot was seen as a round, grayish dark spot within the fibrinous lesion in all eyes. On FFA and OCT, this dot corresponded to the site of leakage. All eyes showed resolution of CSC on follow-up. CONCLUSION: Detection of a dark spot within fibrinous CSC is an important clinical sign that, if present, helps to avoid misdiagnosis, unnecessary diagnostic tests, and incorrect treatment.

Reversible retinal changes in the acute stage of sympathetic ophthalmia seen on spectral domain optical coherence tomography.

To report the changes seen in the photoreceptor layer during the acute phase of sympathetic ophthalmia. Six consecutive patients diagnosed with sympathetic ophthalmia were enrolled in the study. All 6 patients had a fundus fluorescein angiogram and spectral domain optical coherence tomography (OCT) scan carried out at presentation. The outer retinal segment was demarcated on the raster line scan between the external limiting membrane (ELM) and the retinal pigment epithelium (RPE)-choriocapillaris complex. All patients received intravenous methylprednisolone followed by oral corticosteroids 1-1.5 mg/kg/day. The serial follow-up OCT scans taken 48 h after the initiation of treatment, and 1, 2 and 12 weeks later, were studied and compared. The retina inner to the ELM did not show any remarkable structural alteration in any of the eyes. The outer retinal segment demarcated by the ELM and the RPE-choriocapillaris complex showed serous retinal detachment in all the eyes and elongation of photoreceptors could be seen in four eyes. There was a disruption to the continuity of the two inner hyper-reflective bands in all the eyes. A repeat raster line scan performed 48 h after systemic corticosteroid therapy showed a reduction in the height of the serous retinal detachment with elongation of photoreceptors and the protrusion of their apical segments into the serous detachment in 4 eyes. The serous detachment showed a progressive reduction in height following intravenous methyprednisolone therapy in all the eyes over the following week with elongated photoreceptors in all six eyes. After two weeks, none of the eyes showed any residual detachment and this corresponded with the improvement in visual acuity in all the eyes. OCT raster line scans repeated at 4 weeks showed resolution of serous detachment with normal photoreceptor layer and restoration of a third hyper-reflective band (IS/OS junction) in all the eyes. The photoreceptor layer is involved during the acute phase of sympathetic ophthalmia as indicated by the in vivo morphological changes seen on spectral domain OCT. These changes are reversible following systemic corticosteroid therapy thus supporting the hypothesis that prompt and aggressive anti-inflammatory therapy is capable of reversing the photoreceptor changes.

Spontaneous closure of retinal pigment epithelium microrip in the natural course of central serous chorioretinopathy.

PURPOSE: To study the natural course of changes observed in the retinal pigment epithelium (RPE) on spectral domain OCT transverse and RPE fit C-scans corresponding to the leakage point observed on fundus fluorescein angiograms in central serous chorioretinopathy (CSC). METHODS: Thirteen patients with acute CSC were prospectively enrolled and followed up for 6 months. All were examined using Zeiss Cirrus HD-OCT Model 4000. Transverse and RPE fit C-scans corresponding to point of leakage were superimposed on an OCT fundus photograph and correlated with the leakage point on a fluorescein angiogram. The RPE alterations observed at the leakage point were noted at presentation and follow-up. RESULTS: Transverse and RPE fit C-scans showed an irregularity of RPE resembling a 'honeycomb' pattern in 11 (85%) eyes at the point corresponding to the fluorescein leakage site. These were observed as pigment epithelium detachment (PED) on Raster line scan. Six of these 11 eyes (54.5%) showed a disruption/breach in the RPE on transverse C-scan and on RPE fit C-scan. All eyes showed a resolution of subretinal fluid with a closure of microrip, and the honeycombed pattern at the leakage site was replaced with RPE hypertrophy. CONCLUSION: RPE microrips show spontaneous closure in the natural course of CSC.

Morphological changes in the retinal pigment epithelium on spectral-domain OCT in the unaffected eyes with idiopathic central serous chorioretinopathy.

PURPOSE: To report the changes seen in the retinal pigment epithelium (RPE) morphology in the asymptomatic eyes of patients with idiopathic central serous chorioretinopathy (ICSC) using spectral-domain Cirrus (TM) high-definition optical coherence tomography (HD-OCT). METHODS: In a prospective case series, 17 consecutive patients with unilateral ICSC underwent spectral-domain Cirrus (TM) HD-OCT scans for both affected and opposite asymptomatic eye. Three-dimensional single-layer RPE map was studied in both eyes for morphological alterations, and findings were correlated with clinical presentation, fluorescein angiogram, and 5 Line raster scan. Additionally, three-dimensional (3D) single-layer RPE maps done in 111 healthy volunteers served as control. RESULTS: In patients with ICSC, 3D single-layer RPE analysis of asymptomatic eyes showed presence of RPE bumps in 16 (94%) eyes and pigment epithelium detachment (PED) in 2 (11.8%) eyes. The 5 Line raster scan was normal in all eyes. Of 222 normal (control) scans, 18 showed RPE bumps and none showed PED. Conclusions 3D single-layer RPE map showed abnormal pattern in the asymptomatic eyes of patients with unilateral ICSC. SUMMARY: Spectral-domain optical coherence tomography showed morphologic alterations in retinal pigment epithelium in both eyes of patients with idiopathic central serous chorioretinopathy.

Posterior sympathetic ophthalmia: a single centre long-term study of 40 patients from North India.

OBJECTIVE: To report 'posterior sympathetic ophthalmia' in North Indian population as an early manifestation of sympathetic ophthalmia. METHODS: Forty consecutive patients with a diagnosis of sympathetic ophthalmia seen between 1989 and 2004 at our centre were studied for their clinical presentation and disease course. All received systemic corticosteroids and 12 patients, in addition, also received immunosuppressive agents. RESULTS: There were 28 male and 12 female patients with a median age of 29.4 years. In 22 of the 40 sympathizing eyes, the only presenting sign was the fundus lesions without any associated anterior segment inflammation. Only four eyes showed classically described granulomatous anterior uveitis at presentation. The fundus lesions predominately included exudative retinal detachment (29 eyes), yellowish-white mid-peripheral lesions (10 eyes), optic disc oedema (15 eyes), vasculitis (three eyes), and peripapillary choroidal neovascular membrane (two eyes). Over a median follow-up of 5.2 years, recurrences were seen in 12 of 40 (30%) eyes and were mainly in the anterior segment. Over a median follow-up of 5.2 years, a final visual acuity of 20/40 or better could be achieved in 29/36 (80.5%) eyes. CONCLUSION: In the early stage, sympathetic ophthalmia may present only in the posterior segment without any associated anterior segment inflammation and carries a good visual prognosis. Anterior segment inflammation, however, maybe seen during recurrences.

Retinal microaneurysmal closure following focal laser photocoagulation in diabetic macular edema.

OBJECTIVE: To determine the temporal relationship of microaneurysmal dosure following focal laser photocoagulation in diabetic macular edema. PATIENTS AND METHODS: This prospective study included 25 eyes of 23 diabetic patients with clinically significant macular edema. Ten to 20 well-defined microaneurysms were preselected and marked on an enlarged photograph of the prelaser fundus fluorescein angiogram. These preselected microaneurysms were focally lasered and followed up angiographically at 48 hours, 1 week, 3 weeks, 6 weeks, and 12 weeks after photocoagulation. Thereafter, the average time span between photocoagulation and the closure of the microaneurysms was determined. RESULTS: The mean number of preselected microaneurysms at baseline was 18.24 +/- 3.51, which remained the same at 48 hours. However, the mean microaneurysmal count decreased to 11.76 +/- 2.65 (35% reduction) at 1 week, 9.12 +/- 2.53 (50% reduction), 7.12 +/- 2.26 (61% reduction), and 4.56 +/- 1.32 (75% reduction) at 3, 6, and 12 weeks, respectively. The majority of the microaneurysms (35%) closed between 48 hours and 1 week. CONCLUSIONS: The microaneurysmal closure following focal laser photocoagulation is a delayed process. None of the preselected microaneurysms showed closure within 48 hours, and 75% of the preselected microaneurysms closed at the end of 12 weeks.

Retrieval of a dropped corneal button from a vitrectomized eye.

A successful retrieval of a dropped corneal button from an aphakic vitrectomized eye during penetrating keratoplasty is reported. A 52-year-old female patient underwent penetrating keratoplasty for aphakic corneal edema in a vitrectomized eye. The donor button inadvertently dropped into the vitreous cavity and was retrieved successfully. The dropped corneal button was visualized after focusing the operating microscope on the retina. The visualization significantly improved after aspiration of the fluid from the vitrectomized eye. The donor button was picked up by McPherson's forceps and subsequently sutured to the recipient's cornea. Corneal surgeons need to be aware of this rare complication in aphakic vitrectomized eyes and its retrieval after accurate visualization.

Fungal endophthalmitis following cataract surgery: clinical presentation, microbiological spectrum, and outcome.

PURPOSE: To determine the clinical presentation, microbiological spectrum, and outcome in cases of fungal endophthalmitis following cataract surgery. DESIGN: Observational case series. SETTING: Tertiary referral hospital. PATIENTS: Retrospective analysis of 27 cases of smear- and culture-proven fungal endophthalmitis. INTERVENTION: Pars plana vitrectomy in 18 eyes, where the corneal condition did not preclude the same. All eyes received intravitreal amphotericin B and dexamethasone along with systemic antifungal agents. MAIN OUTCOME MEASURES: Functional success: Final visual acuity of 3/60 or better with attached retina. Anatomical success: Final visual acuity of better than light perception with preserved anatomy of globe. RESULTS: The majority of the eyes (22 of the 27) had early onset and diffuse presentation (that is, anterior segment as well as posterior vitreous exudates). Substantial corneal involvement was seen in 14 eyes (51.85%). Aspergillus sp. was the most common isolate. Multivariate analysis using forward stepwise logistic regression showed corneal involvement as the single most important risk factor in determining final visual outcome (P =.0429). CONCLUSIONS: Early onset and diffuse presentation, which mimics bacterial endophthalmitis, stresses the importance of both bacterial and fungal cultures from intraocular fluids to reach a diagnosis apart from the clinical judgment. Corneal involvement was the most important predictor of outcome in cases of fungal endophthalmitis.

PCR-positive tubercular retinal vasculitis: clinical characteristics and management.

BACKGROUND: Inflammation of retinal vessels is a known association of systemic tuberculosis. Patients with retinal vasculitis are subjected to extensive but unrewarding systemic workup. Polymerase chain reaction (PCR) is now commonly used to detect DNA of infective organisms including Mycobacterium tuberculosis. This study was undertaken to characterize the clinical characteristics of PCR-positive tubercular retinal vasculitis, so as to determine the clinical presentation, associated systemic features, management, and course of this form of vasculitis. METHODS: The clinical records of 13 patients seen between 1997 and 1999 with the diagnosis of PCR-positive tubercular retinal vasculitis from the aqueous or vitreous humor were reviewed. Recorded data included age, sex, race, visual acuity, anterior and posterior segment findings, and results of diagnostic evaluations. All received antituberculosis therapy with or without concomitant corticosteroids. Laser scatter photocoagulation was done in eyes with neovascularization. One eye with vitreous hemorrhage was subjected to pars plana vitrectomy. RESULTS: There were 9 (69.2%) male and 4 (30.7%) female patients with a median age of 20 years. The disease was bilateral in seven. The most consistent finding was the presence of vitritis in all the eyes followed by vitreous snowball opacities in 17 eyes (89.4%), neovascularization in 11 eyes (57.8%), retinal hemorrhages in 10 eyes (52.6%), neuroretinitis in 10 eyes (52.6%), focal choroiditis in 9 eyes (47.3%), vitreous/preretinal hemorrhage in 5 eyes (26.3%), and serous retinal detachment in 3 eyes (15.7%). Over a median follow-up of 12 months, all showed resolution of vasculitis with no recurrences. CONCLUSIONS: Polymerase chain reaction-positive tubercular retinal vasculitis had varied associated fundus findings. Its recognition is important so as to order only relevant diagnostic tests.

Efficacy of various laser wavelengths in the treatment of clinically significant macular edema in diabetics.

BACKGROUND AND OBJECTIVE: To compare various laser wavelengths: argon green (514 nm), vs krypton red (647 nm), vs frequency doubled Nd:YAG (532 nm), and vs diode (810 nm), for laser photocoagulation treatment in clinically significant macular edema (CSME) in diabetics. PATIENTS AND METHODS: Four different wavelengths were used to sequentially treat 271 eyes of 164 diabetic patients with CSME. Follow up was conducted for a minimum of 6 months (9.8 +/- 1.3 months). Retreatment was performed if residual edema involving the foveal avascular zone persisted at 3 months. RESULTS: Reduction/elimination of CSME was observed in 93.3% of argon-treated eyes, 88.5% in krypton red group, 92.9% with frequency doubled Nd:YAG, and 84.8% with diode laser with no statistically significant difference between the groups (P > 0.05 for all groups). The number of eyes requiring retreatment was highest with the diode laser having 44.3% of eyes requiring retreatment and least with frequency doubled Nd:YAG having only 15.5% of eyes requiring retreatment (P = 0.0002). CONCLUSIONS: All lasers are equally effective in reducing/eliminating CSME. However, Nd:YAG may have an advantage because of requiring fewer retreatments.

Traumatic lens abscess with chornic endophthalmitis successfully treated with pars plana lensectomy and vitrectomy.

Intralenticular abscess is a rare entity and has been infrequently reported after surgery, metastatic infection, or trauma. We report a case of post traumatic lens abscess with low-grade endophthalmitis following a penetrating eye injury with a splinter of wood. The patient was successfully treated with a pars plana lensectomy and vitrectomy. Despite thorough microbiological investigations, no causative organism could be isolated.

Curvularia lunata endophthalmitis with secondary keratitis.

PURPOSE: To report a case of pseudophakic endophthalmitis with secondary keratitis caused by Curvularia lunata. METHODS: A 40-year-old man presented with a fluffy mass in the anterior chamber with low-grade delayed postoperative inflammation in the right eye. RESULTS: The anterior chamber and vitreous aspirate demonstrated C. lunata. A large corneal infiltrate developed after aspiration of the mass. Treatment with systemic, topical, and intraocular antifungal agents cleared the vitreous, but the cornea perforated. CONCLUSION: Delayed low-grade infection with a fluffy mass in the anterior chamber after cataract surgery can rarely be a clinical presentation of dematiaceous fungal infection. Secondary keratitis may result after a diagnostic aspiration.

Threshold retinopathy of prematurity: ocular changes and sequelae following cryotherapy.

PURPOSE: To determine ocular changes and sequelae following cryotherapy for threshold retinopathy of prematurity (ROP). METHODS: This is a retrospective study of 49 eyes of 26 premature babies with threshold ROP treated with cryotherapy between 1995 and 1998. All eyes included in the study had favourable structural outcome after cryotherapy. Follow-up examination of all babies was done 12 - 62 months (average 28 months) after cryotherapy. Visual axis, fixation pattern, anterior segment examination, cycloplegic refraction and dilated fundus examination with indirect ophthalmoscopy were undertaken in all eyes during follow-up. RESULTS: Posterior pole retinal residuae observed following cryotherapy were tortousity of blood vessels in 32 (65.3%), narrow temporal arcade in 22 (44.89%), temporal crescent in 17 (34.69%), disc drag in 13 (26.53%) and macular heterotopia in 7 (14.28%) eyes. Myopia was observed in 20 (40.82%) eyes and strabismus in 5 (19.23%) babies. The significant risk factor for ocular changes was ROP with more clock hours of involvement (p < 0.05). Higher period of gestation was associated with posterior pole changes (p< 0.05). CONCLUSIONS: All premature babies with threshold ROP treated with cryotherapy require frequent and long-term follow up to look for retinal residuae, refractive status, and ocular motility disorders.