Sero-prevalence of Nipah antibodies among close contacts of the index case during 2019 Ernakulam outbreak.

Introduction: Nipah virus (NiV) infection is a fatal emerging zoonotic disease. Infection with NiV has a wide range of clinical spectrum which can range from asymptomatic cases to acute respiratory distress syndrome (ARDS). The index case of NiV infection of 2019 outbreak in Ernakulam district was a 23-year-old male who presented with features of encephalitis. This study was undertaken to address the subclinical or asymptomatic NiV infection amongst the close contacts of this index case by using NiV-specific Immunoglobulin IgM and IgG antibodies. The index case was first treated in a primary care center. He survived the infection and was discharged after a period of 108 days from the tertiary care facility where he was treated eventually. Methods: Serum samples from 49 close contacts of the index case were collected and tested for anti-NiVIgM and anti-NiVIgG antibodies. The contacts included health care workers including those from the primary care facility, family members, and his friends. Results: Most common type of exposure included physical contact (59.2%), followed by exposure to body fluids (22.4%). Conclusion: None of the 49 contacts tested positive for anti-NiV human IgM and anti-NiVIgG antibodies. There were no subclinical cases amongst the close contacts of Nipah index case during the 2019 Kerala outbreak.

The Synergy between Palmitate and TNF-α for CCL2 Production Is Dependent on the TRIF/IRF3 Pathway: Implications for Metabolic Inflammation.

The chemokine CCL2 (also known as MCP-1) is a key regulator of monocyte infiltration into adipose tissue, which plays a central role in the pathophysiology of obesity-associated inflammation and insulin resistance. It remains unclear how CCL2 production is upregulated in obese humans and rodents. Because elevated levels of the free fatty acid (FFA) palmitate and TNF-α have been reported in obesity, we studied whether these agents interact to trigger CCL2 production. Our data show that treatment of THP-1 and primary human monocytic cells with palmitate and TNF-α led to a marked increase in CCL2 production compared with either treatment alone. Mechanistically, we found that cooperative production of CCL2 by palmitate and TNF-α did not require MyD88, but it was attenuated by blocking TLR4 or TRIF. IRF3-deficient cells did not show synergistic CCL2 production in response to palmitate/TNF-α. Moreover, IRF3 activation by polyinosinic-polycytidylic acid augmented TNF-α-induced CCL2 secretion. Interestingly, elevated NF-κB/AP-1 activity resulting from palmitate/TNF-α costimulation was attenuated by TRIF/IRF3 inhibition. Diet-induced C57BL/6 obese mice with high FFAs levels showed a strong correlation between TNF-α and CCL2 in plasma and adipose tissue and, as expected, also showed increased adipose tissue macrophage accumulation compared with lean mice. Similar results were observed in the adipose tissue samples from obese humans. Overall, our findings support a model in which elevated FFAs in obesity create a milieu for TNF-α to trigger CCL2 production via the TLR4/TRIF/IRF3 signaling cascade, representing a potential contribution of FFAs to metabolic inflammation.

Laser therapy in the management of choroidal breast tumor metastases.

PURPOSE: To evaluate the potential of laser photocoagulation as a method of treating small metastatic lesions of breast carcinoma in the choroid. METHODS: The 10 eyes of 7 patients were treated by Krypton red or argon green laser applications for small choroidal breast carcinoma metastasis with serous detachment of the retina. Before treatment 5 eyes had visual acuity of finger counting and 5 eyes had visual acuity of 6/15 or better. The treatment was repeated once in all eyes, except 1 eye in which it was repeated 3 times. RESULTS: In all eyes, one to two weeks after the treatment the tumor shrunk, the subretinal serous detachment absorbed, the retina flattened, and the visual acuity improved to 6/6-6/21. No reduction in vision was seen after the second treatment until the end of the follow-up period. In 1 eye, new tumors located elsewhere were again twice successfully treated. Patients reported a significant improvement of their quality of vision, as judged subjectively. CONCLUSIONS: Laser treatment is a feasible, easy, rapid, and effective therapy for small choroidal breast carcinoma.

Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients.

PURPOSE: To assess the long-term efficacy of combined vitamin A and E treatment in preventing retinal degeneration in patients with abetalipoproteinaemia (ABL) or homozygous hypobetalipoproteinaemia (HBL). METHODS: Ten patients with ABL and 3 with homozygous HBL who were treated with oral supplements of vitamins A and E were studied. Systemic, ophthalmological and electroretinographic follow-up for a mean of 11.7 years (range 4-20 years) after onset of treatment was evaluated. RESULTS: Despite vitamin A and E treatment, 7 of 10 patients who began treatment prior to 2 years of age and all 3 patients who began treatment later in life manifested unusual fundoscopic pigmentary changes over time. At the end of follow-up, 11 of 13 patients had subnormal mixed cone-rod electroretinogram amplitudes. Seven of 10 patients for whom perimetry was available had mild to severe constriction of the visual fields. CONCLUSIONS: Combined oral vitamin A and E supplementation that is initiated prior to 2 years of age can markedly attenuate the severe retinal degeneration that is associated with untreated ABL or homozygous HBL. Yet, fundoscopic and functional retinal changes do occur despite early initiation of vitamin treatment. Therefore, the adequacy of the present treatment protocol for ABL and homozygous HBL should be re-evaluated.

Retinitis pigmentosa associated with Fuchs' heterochromic uveitis.

OBJECTIVE: To investigate whether the combination of Fuchs' heterochromic uveitis (FHU) and retinitis pigmentosa (RP) in the same patient is coincidental or represents a true association. METHODS: We have examined the frequency of FHU in 338 patients with RP and in 1984 patients who were seen in our primary care ophthalmic clinic because of reasons other than RP. RESULTS: Of 338 patients with RP, 4 (1.2%) had the typical findings of FHU. Three of them had Usher syndrome type II, and 1 had RP simplex. By contrast, only 1 patient in the control group had FHU (5%), and the difference in the frequency of FHU between the 2 groups was significant (P=.002, Fisher exact test). CONCLUSIONS: Fuchs' heterochromic uveitis is associated with RP. Since autoimmune phenomena have been previously described in patients with RP, it is conceivable that RP predisposes to the development of FHU. Arch Ophthalmol. 2000;118:800-802

Mechanisms of photoreceptor death and survival in mammalian retina.

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any other retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial "depletion" stage caused by genetic or environmental insult and a second "late" stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second "late" stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed.

Cone and rod dysfunction in the NARP syndrome.

AIMS: Description of the ophthalmic manifestations of the NARP (neuropathy, ataxia, retinitis pigmentosa) syndrome that is associated with a point mutation in position 8993 of the mitochondrial DNA (mtDNA). METHODS: A mother and her two children, all carrying the 8993 mtDNA mutation, were examined. Two had manifestations of the NARP syndrome. A complete ocular and systemic examination was performed on all three patients. RESULTS: The clinical examination, electroretinogram, and visual fields revealed a typical cone-rod dystrophy in the son, and a typical cone dystrophy in the daughter. The mother had no ocular manifestations of the disease. CONCLUSIONS: NARP is a recently described, maternally inherited mitochondrial syndrome in which a retinal dystrophy, among other abnormalities, is related to a mutation of the mtDNA at nucleotide 8993. This study demonstrates the great variability of the ocular manifestations in the NARP syndrome. It also indicates that the retinal dystrophy in at least some NARP patients affects primarily the cones.

The effect of a new tear substitute containing glycerol and hyaluronate on keratoconjunctivitis sicca.

The purpose of this study was to evaluate the efficacy of LO2A, a newly developed tear substitute containing glycerine and sodium hyaluronate, in the treatment of dry eyes. Twenty-five informed consent patients suffering from keratoconjunctivitis sicca were included. Patients were treated for one week with LO2A in one eye, and with their current tear substitute in the other eye. Rose bengal staining was evaluated on a scale of 0 to 3. Patient satisfaction was graded on a scale of 1 to 5. The average satisfaction score for LO2A was significantly higher compared to the control preparations at 1 week (p=0.0003) and at 2 weeks (p=0.0232). A highly significant reduction in rose bengal staining was demonstrated following 1 week of treatment with LO2A (p<0.0001). The LO2A treated eyes had significantly less staining than control eyes at 1 week (p=0.021) and at 2 weeks (p=0.023). An inverse correlation was found between patient grading and the rose bengal scoring (spearman rank coefficient = -0.49, p<0.001). LO2A showed a beneficiary effect on dry eye patient satisfaction and on rose bengal test, as compared to other tear substitute preparations currently used by these patients.

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling.

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.

Familial café au lait spots: a variant of neurofibromatosis type 1.

Café au lait spots (CALS) are a frequent and one of the early manifestations of neurofibromatosis 1 (NF1). However, there are patients with isolated CALS who do not meet the diagnostic criteria for NFI. There are several reports of families in which CALS are inherited as an autosomal dominant trait, without any other features of NFI. In one reported family with dominantly inherited CALS linkage to the NF1 locus was ruled out. In order to elucidate the relationship between familial CALS and NF1 further, we performed a linkage analysis in a large kindred with 11 subjects with CALS in three generations and established close linkage between CALS and five NF1 intragenic polymorphisms. We propose that in this family the trait of CALS is allelic to NF1, it is fully penetrant, and it does not confer a risk of other NF1 symptoms.

Neurofibromatosis type I (NFI) in Israeli families: linkage analysis as a diagnostic tool.

Linkage analysis of 18 neurofibromatosis type I (NFI) families was performed using intragenic and flanking polymorphic markers. The aims of the analysis were prenatal diagnosis of at-risk fetuses, and of asymptomatic individuals who were relatives of NFI patients. Prenatal diagnosis was performed in 9 pregnancies of 7 families; 5 fetuses were diagnosed as affected. In 6 families with an affected spouse, the request was to identify informative polymorphisms to be used in future pregnancies. Presymptomatic diagnosis was performed in 4 families. One individual, a brother of an NFI patient, was found to have Lisch nodules as the only NFI symptom. Linkage analysis indicated that if this person is a carrier of the NFI gene, he must be a product of intragenic crossover. In 2 individuals with a new NFI mutation, the origin of the NFI-bearing chromosomes was paternal. The same observation was noted by others. A summary of published cases shows that some 90% of the NFI-bearing chromosomes of patients with new mutations were of paternal origin. We therefore suggest that for the purpose of prenatal diagnosis in carriers of NFI new (and unidentified) mutations, the paternal chromosome will be considered as the NFI-bearing chromosome.

Autosomal recessive colobomatous microphthalmia.

Colobomatous microphthalmia was studied in multiple relatives of 5 families. In these families, the disorder was an autosomal recessive trait as opposed to the usual autosomal dominant form of the disorder. A relatively high incidence of this recessive allele is found in the Iranian Jewish community.

Mucolipidosis type IV: a mild form with late onset.

A 16-year-old girl is presented with mild clinical manifestations and late onset of mucolipidosis type IV (MLIV). The patient, an Ashkenazi Jew, has had minor motor difficulties and mild psychological disturbances since early childhood. Her vision began deteriorating at 12 years of age, due to bilateral corneal opacities and retinal degeneration. At present she attends a regular high school, although she is slow and scholastic achievements are lower than average. Electron microscopic examination and biochemical studies were typical for MLIV, namely, abnormal ganglioside retention and typical pattern of phospholipids accumulation. This very mild presentation of MLIV suggests a broader spectrum of heterogeneity of this disorder and raises the possibility that MLIV, at least among Ashkenazi Jews, might be more frequent than estimated hitherto, due to undiagnosed mild patients.

Variability of Stickler syndrome.

Stickler syndrome is a dominantly inherited disorder characterized by ocular and nonocular manifestations. The phenotype of the affected patients is known to be variable. Our study of 3 families and a review of the literature show that the variability is mostly interfamilial while in each family less variability is present. In one family all the patients had high myopia and most developed a retinal detachment at a young age. In the second family the major symptoms were cleft palate and characteristic facial changes in presence of mild ocular changes. In the third family, all patients had a marfanoid habitus, high myopia, and mental retardation. Interfamilial variability coupled with intrafamilial similarities in clinical manifestation may indicate that the so-called Stickler syndrome represents in fact a phenotype and not a single genetic entity.

Corneal subepithelial monoclonal kappa IgG deposits in essential cryoglobulinaemia.

A 60-year-old man suffering from photophobia and visual disturbances was found to have bilateral superficial corneal grey-white gelatinous deposits. An abnormal cold-precipitable serum component was found and characterised as homogeneous IgG-kappa immunoglobulin. Corneal immunohistochemical examination revealed subepithelial IgG-kappa deposits, focally replacing Bowman's layer. The patient underwent superficial keratectomy in both eyes with satisfactory visual results.

Low-vision aids in Stargardt's disease.

Fifteen patients with juvenile macular degeneration fitted with low-vision aids were followed up for a period of two to three years. About 80% of the patients equipped with visual aids used their devices successfully. It appears that in Stargardt's disease, low-vision aids are more useful than in other maculopathies.