Treatment of ocular surface squamous neoplasia with topical Aloe vera drops.

PURPOSE: To report a case of ocular surface squamous neoplasia (OSSN) that resolved with topical Aloe vera eye drop treatment. METHODS: A 64-year-old Hispanic woman with a lesion typical for OSSN in her left eye was followed up with multiple clinical examinations and ocular surface photographs to document changes over time with A. vera-based topical treatment. RESULTS: The patient refused biopsy of her lesion and traditional treatments and, instead, initiated using A. vera eye drops 3 times daily. At follow-up visits, the lesion was noted to regress until it finally resolved 3 months after commencing treatment. No additional topical medications were used, and she has remained tumor free for 6 years. CONCLUSIONS: Ongoing research is warranted because A. vera may represent a new therapeutic class of medications for OSSN treatment.

Age-related alterations in the dynamic behavior of microglia.

Microglia, the primary resident immune cells of the central nervous system (CNS), exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie key functions of immune surveillance and tissue repair. Although age-related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. In this study, we employed live imaging of retinal microglia in situ to compare microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which probably compromise their ability to survey and interact with their environment continuously. We also found that dynamic microglial responses to injury were age-dependent. While young microglia responded to extracellular ATP, an injury-associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser-induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared with young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age-dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age-related neuroinflammatory degeneration.

Exclusion of positional candidate gene coding region mutations in the common posterior polymorphous corneal dystrophy 1 candidate gene interval.

PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is an autosomal-dominant disorder of the corneal endothelium associated with visually significant corneal edema and glaucoma. Statistical genetic analysis of 4 families with PPCD has demonstrated linkage to a 2.4 cM common support interval on chromosome 20 bordered by the markers D20S182 and D20S139. We sought to identify the genetic basis of PPCD linked to chromosome 20 (PPCD1) by screening the 26 positional candidate genes between these markers in a family previously mapped to the PPCD1 region. METHODS: The coding regions of the 26 positional candidate genes mapped to the common PPCD1 support interval were amplified and sequenced in affected and unaffected individuals from a family previously linked to the PPCD1 locus. Nine other genes positioned just outside of the common PPCD1 support interval but within the autosomal-dominant congenital hereditary endothelial dystrophy interval were also screened. RESULTS: Four DNA sequence variants in 3 of the positional candidate genes demonstrated complete segregation with the affected phenotype: p.Thr109Thr (rs6111803) in OVOL2, p.Arg56Gln (novel variant-RPSnovel) in RPS19P1, and p.Thr85Thr (rs1053834) and p.Pro99Ser (rs1053839) in C20orf79. Each of these 4 sequence variants demonstrated significant linkage with the affected phenotype in this family (P = 2.5 x 10 for RPSnovel, rs1053834 and rs1053839; P = 8.6 x 10 for rs6111803). However, we also identified each of these 4 sequence variants in > or = affected control individuals. The haplotype on which the disease-causing mutation is segregating was found to have a population frequency of 4.2% in the CEPH HapMap trios. Although a number of other previously described and novel single nucleotide polymorphisms were identified in the 35 positional candidate genes located within the PPCD1 and congenital hereditary endothelial dystrophy intervals, none segregated with the affected phenotype. CONCLUSIONS: We report the absence of a presumed pathogenic coding region mutation in the common PPCD1 support interval. Although minor alleles of 4 single nucleotide polymorphisms were identified that segregated with the affected phenotype, the relatively high frequency of each minor allele in the general population indicates that none is a candidate for the causal variant for PPCD. Instead, the causal variant is most likely a coding region deletion or a variant in a noncoding region of the PPCD1 common support interval.

Keratoconus associated with corneal stromal amyloid deposition containing TGFBIp.

PURPOSE: To report the identification and characterization of stromal amyloid deposits in patients with keratoconus. METHODS: The excised corneal buttons from 2 patients diagnosed clinically with keratoconus underwent histochemical analysis with Masson trichrome, Congo red, Alcian blue, and periodic acid-Schiff stains, and immunohistochemical analysis for the transforming growth factor beta-induced gene (TGFBI) protein product (TGFBIp), prealbumin, lysozyme, and kappa and lambda light chain expression. After the collection of DNA from both patients, exons 4, 11, 12, 13 and 14 of TGFBI were amplified and sequenced to search for mutations previously associated with dystrophic corneal stromal amyloid deposition. RESULTS: Light microscopic examination of the corneal buttons revealed stromal thinning, epithelial basement membrane abnormalities, and focal disruption of Bowman layer. Multiple stromal deposits were identified that stained red with Masson trichrome, pink with periodic acid-Schiff, and red with Congo red; the Congo red-stained deposits demonstrated birefringence and dichroism with crossed polarizing lenses. Immunohistochemical staining demonstrated reactivity of the stromal deposits with antibodies to TGFBIp but no reactivity with antibodies against prealbumin, lysozyme, or kappa and lambda light chains. Screening of TGFBI exons 4, 11, 12, 13, and 14 revealed 2 previously identified single nucleotide polymorphisms present in the heterozygous state in both individuals but no other coding region variants. CONCLUSIONS: Two cases of keratoconus with clinically unsuspected, presumed secondary stromal amyloid deposition are described. Although TGFBIp is identified in the stromal deposits, no previously reported amyloidogenic mutations are identified in TGFBI in either affected individual, indicating a previously undescribed mechanism of stromal amyloid deposition.