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   Table of Contents - Current issue
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October-December 2018
Volume 13 | Issue 4
Page Nos. 373-524

Online since Wednesday, October 24, 2018

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EDITORIAL  

Targeted screening for predominant CYP1B1 mutations in primary congenital glaucoma Highly accessed article p. 373
Mansoor Sarfarazi
DOI:10.4103/jovr.jovr_232_18  
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ORIGINAL ARTICLES Top

Visual and refractive outcomes and tomographic changes after femtosecond laser-assisted intrastromal corneal ring segment implantation in patients with keratoconus Highly accessed article p. 376
Seyed Javad Hashemian, Nooshin Farshchian, Alireza Foroutam-Jazi, Mohammad Ebrahim Jafari, Mahsa Sadat Hashemian, Seyed Mahyar Hashemian
DOI:10.4103/jovr.jovr_42_17  
Purpose: To evaluate the visual, refractive, and tomography changes after femtosecond laser-assisted intrastromal corneal ring segment (ICRS; Intacs® SK) implantation in patients with keratoconus. Methods: In this prospective interventional case series, Intacs SK ICRSs were inserted using a femtosecond laser into eyes with stage I–IV keratoconus. Visual, refractive, and corneal tomography changes, along with surgical complications, were analyzed 1 week, 2 months, and 6 months postoperatively. Results: The study evaluated 71 eyes of 52 patients (mean age: 27.5 years). Six months postoperatively, the spherical equivalent, mean sphere, and mean cylinder were decreased by 2.07, 1.47, and 1.13 diopters (D), respectively. The mean preoperative uncorrected distance visual acuity (UDVA) increased from 0.87 ± 0.26 to 0.46 ± 0.19 LogMAR and the mean preoperative corrected distance visual acuity (CDVA) increased from 0.55 ± 0.21 to 0.28 ± 0.17 LogMAR (P < 0.001). Flat and steep keratometry decreased by a mean corneal power in the 3-mm zone, and mean anterior elevation decreased by 0.91 D, 2.52 D, and 1.03 microns (P < 0.001), respectively. Among all eyes, 93.0% gained one or more lines of CDVA. Mean internal anterior chamber depth decreased from 3.25 ± 0.33 to 3.14 ± 0.45 mm (P = 0.001), and mean irregularity in the 3-mm zone decreased from 5.63 ± 1.71 to 5.24 ± 1.82 (P = 0.006). However, mean posterior elevation and irregularity in the 5-mm zone did not change significantly. Conclusion: Implantation of one or two Intacs SK segments is safe and effective to treat keratoconus, leading to significant improvement in UDVA, CDVA, and refractive error.
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Ex vivo caprine model to study virulence factors in keratitis p. 383
Swati N Madhu, Kartik Kumar Jha, Annapoorna P Karthyayani, Devarshi Urvish Gajjar
DOI:10.4103/jovr.jovr_131_17  
Purpose: To develop an infectious keratitis model using caprine (goat) corneas and to investigate the expression of virulence factors during infection. Methods: Goat eyes were surface-sterilized and dissected, and the corneas were placed on an agarose-gelatin solid support (0.5% in phosphate-buffered saline) in a 12-well culture plate containing 10% fetal bovine serum-supplemented culture medium for 3 weeks. Cell viability tests (trypan blue and MTT) were performed on the cultured corneas. Corneas were infected with Pseudomonas aeruginosa and Fusarium solani separately. Infection progression was observed via histological analysis and hematoxylin and eosin (H-E) staining. For Pseudomonas-infected corneas, expression of eight virulence genes (exoS, exoT, exoY, alpR, prpL, lasA, lasB, and algD) was determined via quantitative real-time PCR (qRT-PCR) at 48-h and 72-h time-points. For Fusarium-infected corneas, expression of five proteases (C7Z0E6, C7ZFW9, C7Z7U2, C7ZNV5, and C7YY94) was quantified via qRT-PCR at 2, 4, and 8 days after infection. Protease from infected corneas was detected via gelatin zymography. Results: Goat corneas with a viable epithelium could be maintained for 15 days. Pseudomonas infection progressed rapidly, and complete corneal degradation was observed on day 4 after infection. Fusarium infection progressed more slowly. Histological analysis and H-E staining of Fusarium-infected cornea revealed mycelia penetrating all layers of the cornea. qRT-PCR revealed expression of all eight virulence factors, and statistically significant difference in expression of prpL and alpR in Pseudomonas-infected corneas. Expression of C7ZNV5 was highest in Fusarium-infected corneas. Conclusion: Goat corneas can be used to evaluate the expression of virulence factors involved in Pseudomonas and Fusarium infection.
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Real time polymerase chain reaction for hepatitis B screening in donor corneas in the central eye bank of Iran p. 392
Shahram Samiee, Mozhgan Rezaei Kanavi, Mohammad Ali Javadi, Abouzar Bagheri, Sahar Balagholi, Marzieh Sadat Hashemi
DOI:10.4103/jovr.jovr_157_17  
Purpose: The aim of this study was to report the results of the use of real-time polymerase chain reaction (PCR) for the diagnosis of hepatitis B virus (HBV) infection in cornea donors at the Central Eye Bank of Iran. Methods: Between 2014 and 2016, all cornea donors that had negative screening serologic results for hepatitis B (HB) surface antigen, HB surface antibody (Ab), hepatitis C virus Ab, human immune deficiency virus Ab, human T-cell leukemia virus Ab, and syphilis, and positive serology for HB core Ab were subjected to real-time PCR with a detection limit of 400 IU/mL to identify HBV DNA. Positive results for HBV DNA were considered occult HBV infections in these donors. Results: Over the 3-year period, 122 out of 10448 cornea donors had negative screening serologic tests outside of HB core Ab. Of which, 90 cases were subjected to real-time PCR. Occult HBV was detected in 11 cases (12.2%), resulting in the rejection of the corresponding corneas. The remaining 79 cases (87.8%) had negative results for HBV DNA and the corresponding corneas were used for transplantation. Conclusion: Implementation of PCR for the detection of occult HBV in cornea donors is necessary to not only increase the security level of cornea donation but also minimize the rejection rate of donors that have isolated HB core Ab reactivity.
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Association of FOXE3-p.Ala170Ala and PITX3-p.Ile95Ile polymorphisms with congenital cataract and microphthalmia p. 397
Nair Gopinathan Vidya, Darshini Ganatra, Abhay R Vasavada, Sankaranarayanan Rajkumar
DOI:10.4103/jovr.jovr_193_17  
Purpose: To investigate the association of FOXE3-p.Ala170Ala (rs34082359) and PITX3-p.Ile95Ile (rs2281983) polymorphisms with congenital cataract and microphthalmia in a western Indian population. Methods: FOXE3-p.Ala170Ala (c.510C>T) and PITX3-p.Ile95Ile (c.285C>T) polymorphisms were genotyped in 561 subjects consisting of 242 cases with congenital cataract, 52 with microphthalmia, and 267 controls using polymerase chain reaction-restriction fragment length polymorphism. Approximately 10% of samples were randomly sequenced for each single nucleotide polymorphism to confirm the genotypes. The prediction of mRNA secondary structure for polymorphism FOXE3-p.Ala170Ala and PITX3-p.Ile95Ile was performed. Results: A significantly high frequency of T allele and a borderline significance in the frequency of TT genotype of FOXE3-p.Ala170Ala was observed in microphthalmia cases, as compared to controls [T allele: OR: [CI] = 1.8 [1.15-2.72], P = 0.0115; TT: OR [CI] = 2.9 [1.14-7.16], P = 0.0291). The frequency of CC genotype was significantly low in microphthalmia cases when compared to controls (CC: OR [CI] = 0.5 [0.24-0.86, P = 0.0150). There was no significant difference in the allele and genotype frequencies of PITX3-p.Ile95Ile between cases and controls. A slight free energy change was observed in the secondary structure of mRNA between the FOXE3-p.Ala170Ala C-allele (-917.60 kcal/mol) and T-allele (-916.80 kcal/mol) and between PITX3-p.Ile95Ile C-allele (-659.80 kcal/mol) and T-allele (-658.40 kcal/mol). Conclusion: The present findings indicate that FOXE3-p.Ala170Ala 'T' allele and 'TT' genotype could be predisposing factors for microphthalmia while 'CC' genotype might play a protective role against it. A reduction in the free energy change associated with FOXE3-p.Ala170Ala 'T' allele could further contribute towards disease risk.
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P.Gly61Glu and P.Arg368His mutations in CYP1B1 that cause congenital glaucoma may be relatively frequent in certain regions of Gilan province, Iran p. 403
Mansoure Qashqai, Fatemeh Suri, Mehdi Yaseri, Elahe Elahi
DOI:10.4103/jovr.jovr_147_17  
Purpose: To perform a population-based screening of four CYP1B1 mutations—p.Gly61Glu, p.Arg368His, p.Arg390His, and p.Arg469Trp—in the province of Gilan, Iran. Previous studies have shown that CYP1B1 is a cause of disease in approximately 70% of Iranian patients with primary congenital glaucoma (PCG), and that these four mutations constitute the majority of CYP1B1 mutated alleles. The carrier frequencies may even justify premarital screenings. Methods: DNA was extracted from the blood samples of 700 individuals recruited in a population-based epidemiology study in Gilan. Screenings were performed using polymerase chain reaction protocols based on restriction fragment length polymorphism or the amplification-refractory mutation system. For confirmation, the DNA of individuals with mutations was sequenced using the Sanger protocol. Results: Five individuals carried the p.Gly61Glu mutation, and seven carried the p.Arg368His mutation. The p.Arg390His and p.Arg469Trp mutations were not observed in any of the 700 individuals screened. The mutations were not geographically randomly distributed in Gilan; four of the p.Gly61Glu-harboring individuals were from Talesh, and six of the p.Arg368His-harboring individuals were from the eastern regions of Gilan. Conclusion: The frequency of individuals who carry either p.Gly61Glu or p.Arg368His is relatively high in Gilan, and notably high in certain localities within Gilan. We suggest further screenings be performed to definitively assess the need for implementing measures to encourage screening for p.Gly61Glu and p.Arg368His before marriage in Talesh and the eastern regions of Gilan, respectively. Finally, our assessment showed that regional frequencies of CYP1B1 mutations do not necessarily mirror national frequencies.
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Factors associated with conjunctival erosions after ahmed glaucoma valve implantation p. 411
Di Zhou, Xiao Yi Zhou, Alma Michelle Mas-Ramirez, Chaesik Kim, Mark S Juzych, Nariman Nassiri, Bret A Hughes
DOI:10.4103/jovr.jovr_219_17  
Purpose: To investigate the frequency of conjunctival erosions in a series of patients who underwent Ahmed valve implantation in a tertiary referral center and to study risk factors associated with the conjunctival erosions. Methods: This is a single-center, retrospective case-control study of all patients who underwent Ahmed valve implantation between October 2006 and July 2016 at the Kresge Eye Institute in Detroit, Michigan. The series consisted of 306 eyes (277 patients) that underwent Ahmed valve implantation. The rate of conjunctival erosions was determined. Univariate, bivariate, and Cox-proportional hazard analyses were performed to identify factors associated with conjunctival erosions. Results: During the study period, 23 erosions occurred in 306 eyes (7.52%). Aphakia was significantly more common in eyes with erosions (P < 0.05). Aphakia (P = 0.02), uveitic glaucoma (P = 0.03), and longer post-operative use of topical steroids (P < 0.04) significantly increased the risk of erosions based on the Cox model. There were similar rates of erosions with each type of patch graft. No conjunctival erosion was observed after using the modified scleral tunnel method (n = 10). Conclusions: The overall erosion rate was 7.52% in our series. Uveitic glaucoma, aphakia, and longer post-operative use of topical steroids were significantly associated with conjunctival erosions.
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Protective effects of 17β-estradiol on Benzo(e)pyrene[B(e)P]-induced toxicity in ARPE-19 cells p. 419
Ashish U Sapkal, Sonali Nashine, Saffar Mansoor, Vishal R Sharma, Claudio A Ramirez, Rafael Z Migon, Navin K Gupta, Marilyn Chwa, Baruch D Kuppermann, Cristina Kenney
DOI:10.4103/jovr.jovr_16_18  
Purpose: The aim of this study was to examine the effect of 17β-estradiol on Benzo(e)pyrene [B(e)P]-induced toxicity in ARPE-19 cells. Methods: We pretreated ARPE-19 cells with 20 nM and 40 nM 17β-estradiol for 6 hours, followed by addition of 300 μM B(e)P for additional 24 hours. Cell viability was measured using Trypan blue dye-exclusion assay. JC-1 assay was performed to measure mitochondrial membrane potential (ΔΨm). For a quantitative estimation of cell death, apoptotic markers such as caspase-3/7, caspase-9, and caspase-12 were measured. Results: Our results demonstrated that when treated with B(e)P, the viability and ΔΨm of ARPE-19 cells declined by 25% and 63%, respectively (P < 0.05). However, pretreating with 17β-estradiol increased the viability of ARPE-19 cells by 21% (20 nM) and 10% (40 nM) (P < 0.05). Furthermore, the significantly reduced ΔΨm in βE+B(e)P treated cells ARPE-19 cells was restored by pre-treatment with 17β-estradiol- ΔΨm was increased by 177% (20 nM) and 158% (40 nM) (P < 0.05). We further observed a significant up-regulation in the activity of Caspases-3/7, -9, and -12 in B(e)P-treated ARPE-19 cells. However, 17β-estradiol treatment significantly reduced the activity of all apoptotic markers (P < 0.05). Conclusion: In conclusion, our results demonstrate that 17β-estradiol protects ARPE-19 cells against B(e)P-induced toxicity by decreasing apoptosis, preventing cell death, and restoring mitochondrial membrane potential.
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Comparison of retinal and choroidal involvement in sarcoidosis-related chorioretinitis using fluorescein and indocyanine green angiography p. 426
Ala'a El Ameen, Carl P Herbort Jr
DOI:10.4103/jovr.jovr_201_17  
Purpose: To compare the involvement of the retina with that of the choroid in ocular sarcoidosis (OS) using dual fluorescein angiography (FA)/indocyanine green angiography (ICGA). Methods: A retrospective study of 23 patients with the diagnosis of OS was performed. Angiographic signs were quantified following the established FA/ICGA scoring system for uveitis. Results: The choroid was predominantly involved in 19 (82.6%) patients or 87% (40/46) of the eyes, and the retina in 2 (8.7%) patients or 13% (6/46) of the eyes. The mean angiographic score was 7.15 ± 4.5 for the retina (FA) compared to 14.02 ± 4.86 for the choroid (ICGA) (P < 0.0001). In 13% (3/23) of patients, FA did not show retinal inflammation, whereas ICGA was strongly positive, revealing occult choroidal lesions. Conclusion: The choroid is preferentially involved in OS, for which ICGA is the examination of choice. There is a risk of underestimating the global ocular involvement and of missing choroidal involvement if only FA is used. FA/ICGA scoring system allows for quantitative assessment of inflammation in the posterior uvea that occurs in OS; therefore, the system can be useful to quantitatively monitor outcomes in clinical trials.
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Glial cells and retinal nerve fibers morphology in the optic nerves of streptozotocin-induced hyperglycemic rats p. 433
Rafael Aleman-Flores, Blanca Mompeo-Corredera
DOI:10.4103/jovr.jovr_130_17  
Purpose: This study analyzes the structures of optic nerve elements, i.e., glial cells and nerve fibers, in an STZ-induced hyperglycemic animal model. Morphological changes in glial elements of the optic nerve in hyperglycemic and normoglycemic animals were compared. Methods: Transmission electron microscopy, histochemistry, immunohistochemistry, and morphometry were used in this study. Results: Hyperglycemia increased the numbers of inner mesaxons and axons with degenerative profiles. Furthermore, it led to both an increase in the amount of debris and in the numbers of secondary lysosomic vesicles in glial cytoplasm. Hyperglycemia also led to a decrease in glial fibrillary acidic protein expression and an increase in periodic acid-Schiff-positive deposits in the optic nerves of hyperglycemic animals. Conclusion: We conclude that the damage to the structural elements observed in our animal models contributes to the pathogenesis of optic neuropathy in the early stages of diabetes.
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Sympathetic ophthalmia: Experience from a tertiary care center in Northern India p. 439
Rohan Chawla, Monika Kapoor, Aditi Mehta, Koushik Tripathy, Rajpal Vohra, Pradeep Venkatesh
DOI:10.4103/jovr.jovr_86_17  
Purpose: To describe our clinical experience with sympathetic ophthalmia (SO) at a tertiary eye care center in north India. Methods: In this retrospective case series, analysis of the clinical features and visual outcomes of patients diagnosed with SO between March 2012 and March 2016 were performed. Results: Ten male and four female patients (median age, 15.5 years) with SO following penetrating trauma (10 patients) or ocular surgery (four patients) were included. SO developed 2 weeks to 3 years after the insult. Mean presenting visual acuity of the sympathizing eyes was 1.086 (LogMAR). Anterior chamber reaction was documented in all eyes in which it could be assessed (14 sympathizing eyes; five exciting eyes). Neurosensory detachment was seen in 10 of 14 patients (71.5%). Five patients (35.7%) were managed with oral steroids alone, whereas nine (64.3%) were treated with intravenous pulse dexamethasone followed by oral steroids. Inflammation recurred in three patients during steroid tapering, necessitating restarting of steroid therapy with or without additional immunosuppressants. At the last follow-up, all 14 patients were in remission with low-dose oral steroids; seven patients were also on immunosuppressants. At the final follow-up, 12 of 14 (85.7%) sympathizing eyes achieved 20/40 or better visual acuity and three exciting eyes achieved at least 6/24 visual acuity. Conclusion: Although SO is a potentially blinding disorder, early detection and individualized treatment allow most patients achieve good final visual acuity.
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Traumatic ptosis: Evaluation of etiology, management and prognosis p. 447
Sarah Mireles Jacobs, Ariel J Tyring, Arash J Amadi
DOI:10.4103/jovr.jovr_148_17  
Introduction: To investigate whether a systematic approach to subgrouping traumatic ptosis according to etiology can allow for better tailoring of prognosis and treatment. Methods: Retrospective chart review of patients with trauma-related blepharoptosis managed by Oculoplastic surgery specialists at an academic medical center from January 1995 to November 2015. Injury mechanism, eyelid position and function, interventions, and outcomes were reviewed. Results: Of 648 patients treated for blepharoptosis, 55 (8.5%) were traumatic. Careful review revealed 4 subcategories of traumatic ptosis cases: aponeurotic (n = 16), myogenic (n = 18), neurogenic (n = 7), and mechanical (n = 14). Margin reflex distance (MRD1) at presentation was significantly worse for the myogenic subtype (-0.59 mm, SD ±2.09, P = 0.046). The aponeurotic subtype had the best average levator function at presentation (14.29 mm, SD ±2.05), while myogenic had the worst (8.41 mm, SD ±4.94) (P = 0.004). Thirty-five (63.6%) patients were managed surgically. Final MRD1 was significantly different for each subtype (P = 0.163), with aponeurotic 2.63 mm (SD ±1.01), myogenic 1.29 mm (SD ±2.24), neurogenic 1.79 mm (SD ±2.48), and mechanical 2.31 mm (SD ±1.18). There was a significant increase in MRD1 from presentation to final follow up across all groups (P < 0.05). Conclusion: Traumatic ptosis is heterogenous. Systematically evaluating traumatic ptosis cases by trauma mechanism can guide decisions about prognosis and management. Two-thirds of cases were treated surgically, with most patients responding well to conjunctiva-Müller resection or external levator advancement.While all subgroups demonstrated improvement in MRD1 at final follow up, aponeurotic cases had the best prognosis, while myogenic fared the worst and required the longest for maximal recovery.
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Peripapillary retinal nerve fiber layer thickness in normal iranian children measured with optical coherence tomography p. 453
Yadollah Eslami, Zakieh Vahedian, Sasan Moghimi, Fatemeh Bazvand, Haniyeh Salari, Mojtaba Shahabinejad, Afsaneh Malekpoor, Ghasem Fakhraie
DOI:10.4103/jovr.jovr_186_17  
Purpose: This study aimed to measure the peripapillary retinal nerve fiber layer (RNFL) thickness using spectral-domain optical coherence tomography (SD-OCT) in normal Iranian children aged below 18 years. Methods: Peripapillary RNFL imaging was performed in the right eye of normal Iranian children aged below 18 years using Spectralis SD-OCT (Heidelberg Engineering; Vista, CA). The effects of age, gender, cup-to-disc ratio, and spherical equivalent (SE) on global and sectoral RNFL thicknesses were evaluated. Results: A total of 115 eyes were imaged. Approximately 51 (44.3%) of the cases were female children. The mean age was 12.44 ± 2.52 years. The SE of refractive error was 0.39 ± 1.38 diopters (range: −3.00 to +4.5 D). The RNFL thickness measurements in the superior, inferior, nasal, and temporal quadrants were 129.25 ± 14.52, 128.16 ± 13.46, 76.76 ± 10.58, and 69.58 ± 9.94 μm, respectively. The global RNFL thickness was 101.01 ± 7.74 μm. In both univariate and multiple regression analyses, SE was the only determinant of RNFL thickness (all P values < 0.05). Conclusion: OCT analysis can effectively measure RNFL thickness in children, and SE is the only determinant of RNFL thickness in normal Iranian patients aged below 18 years.
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The prevalence of lower eyelid fornix fat prolapse: A diagnostic measure of involutional entropion p. 458
Varajini Joganathan, Chandrashekhara Rai, Mohamed Farag Khalil Ibrahiem, Bijan Beigi
DOI:10.4103/jovr.jovr_164_17  
Purpose: In our experience, lower lid involutional entropion is commonly associated with inferior fornix fat prolapse and non-eversion of the tarsal plate. We aimed to assess the prevalence of this sign as an early diagnostic indicator of lower lid involutional entropion in symptomatic and control groups. Methods: Prospective, comparative, observational case series. Fornix fat prolapse and failure of tarsal eversion in patients with involutional entropion were studied. Fornix fat prolapse was assessed by pulling the lower lid margin to the inferior orbital rim and comparing the meniscus of the protruding fat. The absence of tarsal eversion and lid laxity were also assessed. Patients were reassessed following correction using radiofrequency entropion surgery. Results: Sixty eyes of 50 Caucasian patients with involutional entropion underwent entropion correction. Fornix fat prolapse was found preoperatively in 83.3% (50 eyes), with complete reversal of fat prolapse in 76% (38 eyes) over a mean follow-up of 18.9 months, after successful surgery (P < 0.01). None of the 100 eyes (50 patients) in the control group showed fornix fat prolapse or absence of lower lid tarsal eversion (P < 0.01). Conclusion: There is high prevalence of fornix fat prolapse and failure of tarsal eversion (BB sign) in involutional entropion, with reversal after successful eyelid surgery. The absence of fornix fat prolapse in normal controls suggests that this is an important, underlying anatomical etiology, with diagnostic and prognostic value.
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Awareness of eye health and diseases among the population of the hilly region of Nepal p. 461
Gauri Shankar Shrestha, Ramesh Sigdel, Jyoti Baba Shrestha, Ananda Kumar Sharma, Romina Shrestha, Sanjeeb Kumar Mishra, Sagun Narayan Joshi
DOI:10.4103/jovr.jovr_41_17  
Purpose: To collect information regarding awareness and knowledge of eye health and diseases among the population of the hilly region of Nepal. Methods: In a population-based survey, 1834 participants were enrolled in to the study. Field procedures included the development of a survey questionnaire, field orientation, pretesting, and household data collection. Association between knowledge of eye diseases was derived using the Chi-square test and odds ratios with a 95% confidence interval. A P value of ≤0.05 was considered significant. Results: Most participants were 31–40 years old (33.4%), female (51.1%), of upper caste (43.4%), Hindus (83.3%), received secondary level of education (34.4%), and involved in agriculture (48.6%). Awareness of cataract, night blindness, glaucoma, strabismus, and systemic diseases was 74.6%, 53.4%, 17.4%, 70.8%, and 46.5%, respectively. Knowledge regarding these diseases among those aware was 39.1%, 72.2%, 50.9%, and 92.3%, respectively. Awareness of cataract was significantly higher (88.4%) among higher caste groups (P < 0.001; OR, 4.29; 95% CI, 3.34–5.54), followed by business as an occupation (88.2%; P = 0.001; OR, 2.65; 95% CI, 1.44–4.9). Awareness of night blindness was significantly higher among students (72.6%; P < 0.001; OR, 2.46; 95% CI, 1.65–3.67). Conclusion: There was a general lack of awareness and knowledge of common eye diseases. Improved awareness and knowledge are required for the prevention, early treatment, and access to eye care.
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REVIEW ARTICLES Top

Negative regulators of angiogenesis, ocular vascular homeostasis, and pathogenesis and treatment of exudative AMD p. 470
Mitra Farnoodian, Christine M Sorenson, Nader Sheibani
DOI:10.4103/jovr.jovr_67_18  
Angiogenesis, the formation of new blood vessels from pre-existing capillaries, is very tightly regulated and normally does not occur except during developmental and reparative processes. This tight regulation is maintained by a balanced production of positive and negative regulators, and alterations under pathological conditions such as retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration can lead to growth of new and abnormal blood vessels. Although the role of proangiogenic factors such as vascular endothelial growth factor has been extensively studied, little is known about the roles of negative regulators of angiogenesis in the pathogenesis of these diseases. Here, we will discuss the role of thrombospondin-1 (TSP1), one of the first known endogenous inhibitors of angiogenesis, in ocular vascular homeostasis, and how its alterations may contribute to the pathogenesis of age-related macular degeneration and choroidal neovascularization. We will also discuss its potential utility as a therapeutic target for treatment of ocular diseases with a neovascular component.
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An update on optical coherence tomography angiography in diabetic retinopathy Highly accessed article p. 487
Joobin Khadamy, Kaveh Abri Aghdam, Khalil Ghasemi Falavarjani
DOI:10.4103/jovr.jovr_57_18  
Optical coherence tomography angiography (OCTA) is a novel non-invasive imaging modality for 3-dimensional visualization of retinal and optic nerve capillary networks. In this article, a comprehensive review of relevant original articles in the PubMed database was performed using the search terms “diabetic retinopathy,” “diabetic macular edema,” “diabetes mellitus,” and “optical coherence tomography angiography.” OCTA was found to detect microvascular changes early in diabetes mellitus, even before they become clinically evident. Morphological and qualitative assessment of vascular changes can help to determine the pathophysiological processes, activity, treatment, and follow-up of diabetic retinopathy (DR). Vessel density and foveal avascular zone are the most investigated quantified indices shown to be early predictors of DR, correlated to DR severity and visual function, and useful in predicting response to treatment. OCTA has shown to be a promising alternative to fluorescein angiography in the management of DR. Further studies are warranted to determine the role of OCTA in the routine clinical management of DR.
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PERSPECTIVE Top

The evolution of glaucoma drainage implants p. 498
Frank S Ashburn, Peter A Netland
DOI:10.4103/jovr.jovr_26_18  
The modern glaucoma drainage implant era was initiated with implantation of a plate posterior to the limbus connected to the anterior chamber by a long silicone tube. Non-restrictive (Molteno and Baerveldt implants) and flow-restrictive (Ahmed Glaucoma Valve) implants were developed. With increased clinical experience, variables influencing success and failure of glaucoma drainage implant surgery were better understood. In an iterative process, complications were reduced and indications for drainage implant surgery were broadened. Growth of utilization of glaucoma drainage implants has dramatically increased in recent years. Glaucoma drainage implants have improved the prognosis for surgical success for refractory glaucoma, and have a well-established role in the surgical treatment of glaucoma.
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CASE REPORTS Top

Regressing conjunctival nevus in a child p. 501
Vivian Wing-Man Ho, Matthias Brunner, Rumana N Hussain, Heinrich Heimann
DOI:10.4103/jovr.jovr_215_17  
Purpose: To report a case exhibiting drastic regression of a conjunctival nevus in a child. Case Report: Spontaneous regression of conjunctival nevus is uncommon. We report the case of a nine-year-old Caucasian boy presenting a conjunctival-pigmented lesion situated at the plica semilunaris that underwent a significant reduction in size and color over a period of 15 months. Conclusion: Conjunctival nevus in children is common but regression is rare, especially at the plica. This information could form an important part of the consent process when choosing between observation and surgical excision in the management of a small conjunctival lesion with no suspicious clinical features; since the latter invasive treatment involves risks such as infection, scarring and the possible risk of general anesthesia in children.
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Burkholderia cepacia endophthalmitis: An unusual presentation p. 504
Amarendra Deka, Mir Alam Siddique, Simanta Pradeep Saikia
DOI:10.4103/jovr.jovr_194_16  
Purpose: To report three cases of Burkholderia cepacia endophthalmitis following uneventful phacoemulsification surgery. Case Report: Three cases presented with blurriness of vision 2 to 3 weeks following phacoemulsification. Vitreous culture confirmed the diagnosis. Pars plana vitrectomy with intravitreal injection of vancomycin (1 mg/0.1 ml) and ceftazidime (2.25 mg/0.1 ml) was performed. Despite several modalities of treatment, 2 cases did not respond to intravitreal antibiotics and vitrectomy. The first case ended up with phthisis bulbi and the second case underwent evisceration. One case improved after intravitreal injection of the first dose of antibiotic. Conclusion: B. cepacia endophthalmitis is rare and difficult to treat. More studies are necessary to understand the course and outcome of the infection.
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Optic nerve cysticercosis at the orbital apex presenting as optic neuritis p. 508
Neha Goel
DOI:10.4103/jovr.jovr_251_16  
Purpose: To describe an unusual presentation of ocular cysticercosis and highlight the role of imaging in diagnosis. Case Report: A 33-year-old female presented with loss of vision in her right eye and features suggesting optic neuritis. Magnetic resonance imaging (MRI) of the brain and orbits revealed a cystic lesion with peripheral rim enhancement in the optic nerve substance at the orbital apex. An enzyme-linked immunosorbent assay test for cysticercosis further established the diagnosis as optic nerve cysticercosis. She was treated with oral albendazole and steroids, resulting in remarkable improvement in visual acuity and resolution of the lesion. Conclusion: A high index of clinical suspicion along with appropriate imaging methods can help diagnose rare presentations of ocular cysticercosis. With timely management, successful outcomes can be obtained.
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Bilateral proptosis in a child: A rare presentation of acute lymphoblastic leukemia p. 511
Pon Ramya Sivaperumal, Sneha Magatha Latha, Sowmiya Narayani, Julius Scott
DOI:10.4103/jovr.jovr_2_16  
Purpose: Acute lymphoblastic leukemia (ALL), a common hematological malignancy observed in children, typically presents with fever, pallor, easy bruising, hepatosplenomegaly and lymphadenopathy. However, when ALL manifests with unusual signs and the blood counts and peripheral smears are normal, it causes a diagnostic dilemma. Case Report: We report a 5-year-old boy who presented with bilateral proptosis as the initial manifestation of ALL. He presented with fever and bilateral knee pain attributed to a fall while playing. There was a history of progressive bilateral proptosis for a 3-month period not associated with any other complaints such as fever, eye pain, redness, or tearing. Thyroid function tests were normal. Blood counts acquired upon proptosis presentation were normal. When he presented to us three months later, blood counts revealed a pancytopenia but the peripheral smear showed no abnormal cells. Magnetic resonance imaging of the brain and orbits was normal. Bone marrow aspirate flow cytometry confirmed the diagnosis of B cell acute lymphoblastic lymphoma. Conclusion: Ophthalmologists should be aware of the unusual ophthalmologic manifestations of acute leukemia, as they may precede overt leukemia and cause diagnostic dilemmas. Knowledge about the rare and isolated extramedullary manifestations of ALL facilitates early diagnosis and thereby improves prognosis.
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PHOTO ESSAYS Top

Multiple pit defects of unknown etiology in a foldable hydrophobic intraocular lens p. 514
Ahmed Thabit, Zisis Gatzioufas, Cameron McLintock, Mohamed Elalfy, Samer Hamada
DOI:10.4103/jovr.jovr_118_17  
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Resolution of photoreceptor layer damage in multiple evanescent white dot syndrome p. 516
Francesco Pellegrini, Emanuela Interlandi, Carlos Pavesio
DOI:10.4103/jovr.jovr_125_17  
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Evolution of a retinal hemorrhage p. 518
Mitch J Hargis, Rod Foroozan
DOI:10.4103/jovr.jovr_204_18  
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LETTERS Top

Intraocular pressure after myopic photorefractive keratectomy p. 520
Maddalena De Bernardo, Nicola Rosa
DOI:10.4103/jovr.jovr_209_17  
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Author's reply p. 521
Farid Karimian, Amir Faramarzi, Sahba Fekri, Hossein Mohammad-Rabei, Danial Najdi, Azadeh Doozandeh, Siamak Delfaza-Baher, Mehdi Yaseri
DOI:10.4103/jovr.jovr_217_18  
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Patterns of uveitis at a tertiary referral center in Northeastern Iran p. 522
Mahmood Dhahir Al-Mendalawi
DOI:10.4103/jovr.jovr_89_18  
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Author's reply p. 524
Seyedeh Maryam Hosseini, Nasser Shoeibi, Raheleh Ebrahimi, Mehdi Ghasemi
DOI:10.4103/jovr.jovr_218_18  
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