Trachomatous Scarring Research Articles

A Survey of Trachoma: The Histopathology and the Mechanism of Progressive Cicatrization of Eyelid Tissues

The aim of this study is to demonstrate the spectrum of conditions encompassed by the term ‘trachomatous cicatrization of eyelid tissue’, to discuss the mechanisms of scar tissue formation and to describe sequelae in this potentially blinding condition. Specimens of eyelid tissues were taken from 27 upper eyelids of 21 patients with entropion who underwent surgical procedures and 2 post-mortem upper eyelids with severe trachomatous entropion. Upper palpebral conjunctival swabs and biopsy specimens were taken from 5 patients with active trachoma and they were examined by fluorescence microscopy and routine histopathological methods. Conjunctival impression cytology samples were collected in all patients. In specimens taken from patients with active trachoma the inflammatory infiltrate was organized as lymphoid follicles in the underlying stroma and impression cytology showed cytoplasmic elementary bodies. In specimens taken from patients with scarring trachoma light microscopy studies showed subepithelial fibrous membrane formation, squamous metaplasia and loss of goblet cells, pseudogland formation in conjunctiva, degeneration of orbicularis oculi muscle fibres, subepithelial vascular dilatation, localized perivascular amyloidosis and subepithelial lymphocytic infiltration. Accessory lachrymal glands and the ducts of glands were compromised by subepithelial infiltration and scarring. The contraction of the subepithelial fibrous tissue formed by collagen fibres and anterior surface drying are the main factors contributing to the chronic cicatrization and entropion formation.

Inherited variability of tumor necrosis factor production and susceptibility to infectious disease.

Tumor necrosis factor (TNF) is a critical mediator of host defense against infection but may cause severe pathology when produced in excess. Individuals vary in the amount of TNF produced when their peripheral blood mononuclear cells are stimulated in vitro, and family studies indicate that much of this variability is genetically determined. Since the TNF response to infection is partly regulated at the transcriptional level, TNF promoter polymorphisms have been the subject of intense interest as potential determinants of disease susceptibility. A single nucleotide polymorphism at nucleotide -308 relative to the transcriptional start site has been associated with susceptibility to severe malaria, leishmaniasis, scarring trachoma, and lepromatous leprosy. Some experimental data indicate that this polymorphism acts to upregulate TNF transcription, but this remains controversial. Detailed analysis of multiple genetic markers at this locus and more sophisticated investigations of TNF transcriptional regulation, in different cell types and with a wide range of stimuli, are required to understand the molecular basis of these disease associations.

Antibody response to the 60-kDa chlamydial heat-shock protein is associated with scarring trachoma.

To determine if serum antibody response to the 60-kDa chlamydial heat-shock protein (Chsp60) was associated with scarring trachoma, responses to Chlamydia trachomatis and to Chsp60 from 148 Gambian subjects with trachomatous scarring and from 148 controls without clinical evidence of disease from trachoma-endemic communities were characterized. Chsp60 response was found in 32% of cases and 16% of controls (P < .001). Although C. trachomatis titer was also higher in cases than controls, the prevalence of Chsp60 response between the 2 groups remained significantly different after stratifying for C. trachomatis titer (weighted odds ratio [OR] = 2.1, P = .02). Chsp60 response and C. trachomatis serovar A titer of > or =128 were independently associated with scarring trachoma. The presence of HLA class II allele DRB1*0701 was positively correlated with Chsp60 response (OR = 2.6, P = .02), and DQB1*0301 and DQB1*0501 were negatively associated (OR = 0.42, P < .001; OR = 0.55, P = .46, respectively).

Characterization of B-cell responses to Chlamydia trachomatis antigens in humans with trachoma.

The circulating B-cell responses to Chlamydia trachomatis of 60 children and 34 adults in The Gambia were characterized in a cross-sectional study of different grades of trachoma, using the enzyme-linked immunospot (ELISPOT) assay. Antibody-secreting cells (ASCs) specific to chlamydial major outer membrane protein (MOMP), heat shock protein 60, and whole elementary bodies were detected in children with no evidence of ocular disease, and the immunoglobulin (IgA) response was significantly increased in those with follicular trachoma. In marked contrast, children with the most intense ocular inflammation paradoxically had an almost completely absent B-cell response of all isotypes and to all chlamydial antigens, but with normal serum IgG and IgA responses, which was even lower than in the group with no ocular inflammation. Adults with or without evidence of trachomatous scarring had equivalent numbers of circulating B cells, principally IgA, to all chlamydial antigens. Plasmablasts secreting antibodies to MOMP were present in the urine of children in the absence of urogenital infection detectable by PCR, and relative numbers were 8 to 25 times higher than in blood, suggesting site-specific homing within a common mucosal immune system. These results suggest that ELISPOT assay of ongoing B-cell responses detects suppression of chlamydia-specific IgA ASCs during the proinflammatory response to ocular chlamydial infection seen in intense trachoma, which may play a role in tissue damage leading to trachomatous scarring.

Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid.

Tumor necrosis factor alpha (TNF-alpha) may play a central role in the disease pathogenesis which occurs as a consequence of chlamydial infection. To investigate the importance of TNF-alpha gene promoter polymorphisms and TNF-alpha levels in tear fluid in scarring trachoma, a large matched-pair case-control study was performed in The Gambia. The -308A allele was present in a higher proportion of patients (28.4%) than controls (18.4%), with an increasing association for homozygotes (chi2 for trend, P = 0.032; allele frequency, 0.163 in patients and 0.099 in controls; chi2, P = 0.025). For the -238A allele, the association was similar but not significant. The disease association was highly significant when the number of either -308A or -238A sites in an individual was considered (P = 0.003). TNF-alpha promoter alleles are tightly linked to some HLA class I and II alleles, but multivariate analysis confirmed that the disease associations were independent of HLA, although a class I allele, A*6802, is also associated with disease. TNF-alpha was more frequently detected in tear samples from patients (27.6%) than from controls (15.9%), increasingly so for higher levels of detectable TNF-alpha (P = 0.015). Among patients, detectable TNF-alpha in tears was highly associated with the presence of ocular chlamydial infection (P < 0.001). The results indicate that TNF-alpha plays a major role in the tissue damage and scarring which occurs as a consequence of Chlamydia trachomatis infection.

HLA class I and II polymorphisms and trachomatous scarring in a Chlamydia trachomatis-endemic population.

Immune responses to Chlamydia trachomatis contribute to protection from infection and to immunopathologic disease. To test whether subjects' HLA class I (A, B, and Cw) or class II (DRbeta1 and DQbeta1) types influence risk of trachomatous scarring from chronic infection with C trachomatis, 153 cases and pair-matched controls in Gambia were studied. No HLA type was associated with protection from scarring, indicating that protective immune responses are not limited to only one or a few HLA-restricted epitopes in C. trachomatis antigens. One class I antigen, HLA-A28, was significantly more common among cases than controls (25.8% vs. 15.9%, respectively; McNemar's odds ratio [OR], 1.88; 95% confidence interval [CI] = 1.01-3.49; P = .046). In DNA subtyping of the A28 specificity, the A*6801 allele was equally common among cases and controls, but the A*6802 allele was significantly overrepresented among cases (McNemar's OR, 3.14; 95% CI = 1.32-7.44; P = .009). This association may be due to an immunopathologic HLA-A*6802-restricted cytotoxic T lymphocyte response.

Penetrating keratoplasty in the West Bank and Gaza.

Four hundred and sixteen penetrating keratoplasties performed at St John Ophthalmic Hospital, Jerusalem, between January 1988 and July 1992 were reviewed retrospectively. The leading indications were keratoconus, microbial keratitis, trachomatous corneal scarring and herpes simplex keratitis. After a mean follow-up of 12.4 months (> 1-48 months) 79.8% of the grafts remained clear. The results in terms of graft clarity and visual improvement varied among the different diagnostic groups. No relationship was found between donor age, cadaver time or storage time and graft survival. This series demonstrates the viability of penetrating keratoplasty in this area of low economic development but highlights the need for strict patient selection to ensure optimal use of scarce donor material.

Anatomical Factors Influencing Development of Trichiasis and Entropion in Trachoma

There has been no published investigation into the reasons why some patients with severe trachomatous conjunctival scarring develop entropion and trichiasis while others do not. In a population of leprosy patients with severe trachomatous conjunctival scarring the authors found that lagophthalmos correlated with the absence of trichiasis and entropion. We suggest that orbicularis oculi muscle function, as well as other anatomical variations among individuals, may contribute to the development of trachomatous entropion and trichiasis in patients with conjunctival scarring.

Cell-mediated Immunity in Trachomatous Scarring: Evidence from a Leprosy Population

There is limited understanding of the mechanisms that mediate immunity after infection by Chlamydia trachomatis. Since it is known that the clinical course of leprosy is related to cell-mediated immunity and that such immunity contributes to the development of trachomatous conjunctival scarring, the authors examined patients to determine if there might be an association between leprosy status and trachomatous conjunctival scarring. Leprosy patients registered at Shashemane Hospital were interviewed, examined, and patients with siblings residing in the vicinity were asked to return for further clinical examination. A subsample of sibships was selected for laboratory evaluation of cell-mediated immunity, measured by lymphocyte proliferative responses in vitro to stimulation by mycobacterial antigens. Conjunctival scarring was less severe in multibacillary leprosy patients (with suppressed cell-mediated immunity) than in their healthy siblings and more severe in paucibacillary leprosy patients (with enhanced cell-mediated immunity) than in their healthy siblings. The mean lymphocyte proliferative responses to mycobacterial antigens were greater in the sibling (whether leprous or healthy) with more severe conjunctival scarring, regardless of type of leprosy. The specific cellular immune responses to Mycobacterium leprae and p65 antigen in patients with increased conjunctival scarring provide evidence that early in the course of infection with C. trachomatis, factors related to an individual's cellular response are crucial to the development of conjunctival scarring. A delayed-type hypersensitivity reaction ("reversal reaction") found in paucibacillary leprosy patients could contribute to the increased trachomatous conjunctival scarring in these patients.

Risk factors for trichiasis in women in Kongwa, Tanzania: a case-control study.

Women are at a greater risk compared to men for blinding complications from trachoma. In order to evaluate risk factors in women, 205 cases of trichiasis (TT) were selected from 11 villages in rural Tanzania. Each case of trichiasis was matched to two women of the same age and from the same village, who had no clinical signs of trachoma. Factors associated with trichiasis in a conditional logistic regression included history of trichiasis in the women's mother (odds ratio [OR] = 3.6; 95% confidence interval [CI]: 2.0-6.5); sleeping in a room with a cooking fire during childbearing years (OR = 1.8; 95% CI: 1.2-2.8); a home of wood and earth during childbearing years (OR = 2.1; 95% CI: 1.3-3.3); no adult education classes (OR = 2.2; 95% CI: 1.4-3.4); and five or more deaths among her children (OR = 2.6; 95% CI: 1.3-5.1). Detailed measures of prolonged exposure to child care as a young girl and as a mother showed no significant difference between cases and controls. Results from this study characterize women at high risk for severe disease and eventual blindness in a trachoma endemic area.

Wolfring Dacryops

A unique series of 13 cases of ductal cysts of the accessory lacrimal glands of Wolfring is presented. Once appreciated, they are an easily recognized clinical entity. The 13 cases were verified histologically as arising from ductal epithelium. Biochemical analyses for serum and cyst fluid concentrations of IgA, IgG, and IgM were performed on three of the cases. Histologic staining of the cyst wall using monoclonal antibodies to immunoglobulins was performed on one case. All patients had evidence of extensive trachomatous scarring. High levels of IgA were found in the cyst fluid, consistent with an active secretory mechanism. Monoclonal antibody staining suggested a significant role for paraductal IgA-secreting plasma cells. The formation of a ductal cyst appears to require two successive, inter-related events. The first is an ongoing active secretory process, and the second is an occlusion of the duct. The sequential occurrence of these two events is forwarded as the explanation of dacryops formation. Excision using a conjunctival approach is recommended. A small strip of tarsal border should be removed with the cyst to prevent cyst rupture. The excretory ducts of the Wolfring glands exit through this area.

Anatomical factors influencing development of trichiasis and entropion in trachoma.

There has been no published investigation into the reasons why some patients with severe trachomatous conjunctival scarring develop entropion and trichiasis while others do not. In a population of leprosy patients with severe trachomatous conjunctival scarring the authors found that lagophthalmos correlated with the absence of trichiasis and entropion. We suggest that orbicularis oculi muscle function, as well as other anatomical variations among individuals, may contribute to the development of trachomatous entropion and trichiasis in patients with conjunctival scarring.

T Cells and Trachoma: Their Role in Cicatricial Disease

Frozen sections of tarsoconjunctival biopsies with trachomatous scarring from 14 black adults undergoing corrective surgery for trichiasis, and "normal" tissue from three postmortem controls, were immunohistochemically stained for the major T- and B-cell subsets, and for macrophages and monocytes. T cells outnumbered B cells by 2 to 17 times, and macrophages and monocytes by approximately 20 times in all specimens. Biopsies were categorized as “inflamed” if a cumulative inflammatory score of cellular staining in the substantia propria with CD4, CD8, and OKM1 monoclonal antibodies was greater than that of control tissues. CD4+ lymphocytes predominated over CD8+ lymphocytes in 5 of 7 inflamed biopsies, whereas CD8+ lymphocytes predominated over CD4+ lymphocytes in 5 of 7 noninflamed biopsies. Lymphoid aggregates were present in five inflamed biopsies, but lacked germinal centers, centrally located B cells, or parafollicular T cells typical of the acute stage of trachoma. CD4+ and CD8+ lymphocytes also were observed in the epithelium and lumen of Meibomian glands. These observations indicate that the inflammatory infiltrate of the tarsoconjunctiva in the cicatricial stage of trachoma is comprised predominantly of T cells, and suggests that T cells may be involved in the genesis of tarsal thickening and conjunctival scarring seen in the later stages of trachoma.

Avoidable blindness.

The vast majority of the world's 42 million blind are needlessly impaired. Epidemiologic studies are providing important insights into the cause of cataracts and provision of surgical services; ecologic approaches to the control of trachomatous corneal scarring; treatment and prevention of onchocerciasis; and early diagnosis and treatment of xerophthalmia among others. Continued research and application of existing knowledge can have a dramatic impact on the sight and lives of millions of people.

Leprosy in a trachomatous population.

In an Egyptian leprosy hospital, 17% of 133 patients had a visual acuity of less than 3/60. Corneal opacity, phthisis bulbi, and cataract accounted for 85% of blindness. Leprosy and trachoma together produce blinding corneal opacity by exposure, leprous keratitis, and trichiasis and entropion. Inturned lids, a late result of conjunctival scarring due to childhood trachoma, were less frequent in patients with lepromatous leprosy than in patients with tuberculoid leprosy; because conjunctival scarring from trachoma depends on cell-mediated immunity, patients with lepromatous leprosy may not have had severe trachomatous scarring develop due to their lifelong abnormality in cellular immunity. In patients with leprosy, even when complicated by trachoma, simple measures to prevent or restore vision include medical treatment of leprosy, surgical correction of lid deformities, sector iridectomy for constricted pupils or central corneal opacities, and cataract extraction.

Repair and Reconstruction in the Orbital Region

Part 1 Eyelids - a partial thickness: primary repair secondary contrature tissue loss - superficial tissue loss - deep tissue loss in the preiorbital regions the conjuntiva. Part 2 Eyelids - full thickness: primary and secondary repair reconstruction of the eyelids reconstruction of the upper lid Switch flap reconstruction of the upper lid in severe scarring (trachoma), S.Elroy Pereira reconstruction of both eyelids reconstruction of the eyelids in the absense of the eye surgery of the medical canthus surgery of the lateral canthus the lacrical system, Richard A.N.Welham the eyebrows. Part 3 Miscellaneous: the eyesocket, L.Vistnes post-enucleation anopthalmos and microphthalmos orbital wall trauma, Ian T.Jackson enopthalmos, Ian T.Jackson entropion, trichiasis and ectropion, J.R.O.Collin ptosis, Cromwell and C.Beard congenital ptosis - Mullers muscle and the levator antagonists epicanthus, telecanthus, bleparophimosis and related conditions craniofacial malformations involving the orbital region, Ian T.Jackson congenital colobomas exenteration of the orbit techniques for transfer of resurfacing materials.

CORNEAL TRANSPLANTATION

TABLE OF CONTENTS Prognosis and Graft Clarity Operative Technique Analysis of Results Summary and Conclusions References Statistical Tables Keratoconus Fuchs's Dystrophy Groenouw's Dystrophy Leucoma Keratitis Trachomatous Scarring Ulcers and Ulcer Scarring Scarring (Nonspecific) Chemical Burns and Explosion Injuries Miscellaneous 11. Relation of Diagnosis to Operative Result THE WAVE of enthusiasm over the promise of keratoplasty during the 1940's, particularly in the United States, raised many exaggerated hopes. Excessive publicity attendant on the establishment of eye banks misled both the public and some members of the medical profession as to the potentialities of the corneal graft technique.* The need was apparent for careful evaluation of large series of corneal graft cases to answer these specific questions: When should a corneal graft be done? What is the criterion of a successful operation? What is the probability of success in unselected series of cases? In selected cases? Elschnig,6Filatov,7Thomas,10