Skin biopsies in the evaluation of atypical optic neuropathies

Patients with atypical clinical presentations of common optic neuropathies such as optic neuritis (ON), anterior ischemic optic neuropathy (AION), or optic neuropathy of unknown etiology (UON) are difficult to distinguish from inflammatory autoimmune optic neuropathy (AON) which is typically associated with a poor visual prognosis, unless treated with high doses of corticosteroids and/or immunosuppressive agents. The authors retrospectively evaluated 34 patients [AON (n = 12); AION (n = 5); ON (n = 9); UON (n = 8)] with visual loss which deteriorated over weeks to months or followed an atypical course, for the presence of immunological markers suggestive of AON. These markers included serological testing for antiphospholipid (APA) and antinuclear (ANA) antibodies, and evaluation of histopathologic and immunofluorescent staining of skin biopsies. All patients underwent a skin biopsy. Four of the 12 patients with AON had urticarial cutaneous lesions which revealed leukocytoclastic and/or lymphohistiocytic vasculitis. Seven of the remaining eight AON patients had skin biopsies of non-lesional skin which revealed immunoreactant deposition. Seven of the 21 skin biopsies obtained from the non-AON patients had findings of vacuolization or mild perivascular infiltration of lymphocytes (n = 5) and immunofluorescent deposits (n = 2). Abnormal skin biopsies (92%;p = 0.0009) and circulating APA (82%; p = 0.013) were common in AON patients while ANA was not statistically increased in AON patients (p = 0.06) when compared to the remaining patients as a whole. AON patients typically demonstrate evidence of systemic autoimmune involvement, as manifested by cutaneous abnormalities such as urticarial vasculitis and/or immunoreactant deposition and circulating APA. These may serve as markers for identifying AON patients who may be treated with immunomodulatory agents.     

Preliminary serological studies comparing immunofluorescence assay with radioimmunoassay

We assayed serum from 12 patients with untreated cicatricial pemphigoid affecting the conjunctiva for circulating autoantibodies directed against the epithelial basement membrane zone. We employed a conventional indirect immunofluorescence assay, with monkey esophagus and human conjunctiva as substrates, and compared the results with those obtained employing a radioimmunoassay measuring antibasement membrane zone antibody binding to COLO-16 and to SCaBER tumor cell lines. The indirect immunofluorescence assay on normal human conjunctival substrate detected circulating antibodies to conjunctival epithelium in 6 of 12 CP patient serum specimens. Monkey esophagus failed to detect antibodies to the epithelial basement membrane zone. In contrast, autoantibodies were detected in all 12 specimens by the radioimmunoassay. Specificity, as demonstrated by appropriate controls and assay of normal human serum, was 100%. These results demonstrate that radioimmunoassay employing COLO-16 or SCaBER cells is an exquisitely sensitive and specific assay for detection of circulating antibasement membrane antibodies in patients with cicatricial pemphigoid affecting the conjunctiva.     

Rapid Diagnosis of Chlamydial Conjunctivitis in Laboratory

Purpose: To evaluate the techniques of rapid and accurate diagnosis of chlamydialconjunctivitis.Methods: Total 100 conjunctivitis patients (200 eyes) were studied. Twenty-two of100 cases were diagnosed as chlamydial conjunctivitis. The infected epithelia werescraped from tarsal conjunctiva of both eyes and stained separately with Giemsa (100cases) and immunofluorescence (anti-chlamydial antigen monoclonal antibody, 100cases).Result: In immunofluorescent staining, 38 cases were seen positive staining and 62were negative. In Giemsa staining, 29 were positive, and 71 were negative. In 22 caseswith clinical diagnosis of chlamydial conjunctivitis, 13 cases were confirmed, and 9were excluded by immunofluorescent staining. Technically, immunofluorescent andGiemsa stain takes 45 and 40 minutes, respectively.Conclusion: Comparing to Giemsa stain, 38 of 100 scraping specimens were positive(38% ) by immunofluorescent staining, 29 of 100 per cent were positive by Giemsastaining. Giemsa staining takes 5 minutes less     

Glaucoma in patients with ocular cicatricial pemphigoid

This retrospective review of 111 patients with ocular cicatricial pemphigoid (CP) identifies 29 patients (26%) with glaucoma. Twenty-seven of these patients had a history of glaucoma for a mean of 11.3 years before the diagnosis of CP was made. Most had advanced glaucoma, with a long history of medication use, optic nerve damage, and visual field loss. Patients with CP and glaucoma were more likely to manifest continued high-grade conjunctival inflammation than those with CP alone despite treatment for CP (P less than 0.05). Possible mechanisms including genetic susceptibility to both diseases, drug-induced conjunctival cicatrization, and CP-induced alterations in aqueous outflow are discussed. Physicians who care for patients with CP should remain mindful of the possible coexistence or development of glaucoma in this group of patients. Patients with glaucoma and chronic conjunctivitis of uncertain etiology should be referred for evaluation by physicians experienced in the detection and management of CP.     

The value of biopsies in the evaluation of chronic progressive conjunctival cicatrisation

Background: Chronic progressive conjunctival cicatrisation is poorly understood, and therapy of this condition remains difficult. This study assessed the value of immunohistochemical investigations in the evaluation of patients who present with chronic cicatrising conjunctivitis similar to cicatricial pemphigoid (CP) Methods: Bulbar conjunctival biopsies from 36 patients with acute (n = 5), subacute (n =13) and chronic (n=18) ocular disease were studied. The biopsy was retaken in 7 patients to evaluate the present immunological findings in comparison with a biopsy more then 5 years ago. All the specimens were investigated for the presence of immunoglobulins and complement at the epithelial basement membrane, and the phenotype of the inflammatory cellular infiltrate was analysed. Twenty-nine patients were evaluated for the presence of circulating IgG-anti-basement membrane zone antibodies Results: CP was confirmed by immunoglobulins and/or complement deposition at the epithelial basement membrane in 11 patients (31%). IgA was found to be the most frequent deposit. Eleven CP patients, mainly those with active or burnt-out disease, showed absence of immunoglobulins and/or complement at the conjunctival basement membrane. In 14 of 36 patients, conjunctival cicatrisation was subsequently felt to be caused by conditions other than CP. The cellular phenotype in the subepithelial conjunctiva was unspecific, but in CP the disease activity was reflected by the number of neutrophils and macrophages. Circulating IgG antibodies were found in none of the patients' serum Conclusion: Immunoglobulin and/or complement deposition at the epithelial basement membrane confirms the diagnosis of mucous membrane pemphigoid. Their absence, however, does not rule it out and is a frequent feature in very active conjunctival disease or after immunosuppressive treatment. The analysis of the cellular phenotype in mucous membrane pemphigoid may be useful in the assessment of disease activity but does not help in determining the underlying disease process causing the cicatrising conjunctivitis     

早期原发性开角型青光眼彩色图形视觉电生理改变分析

目的 探讨早期原发性开角型青光眼彩色图形视网膜电图（ＣＰ－ＥＲＧ）,彩色图形视觉诱发电位（ＣＰ－ＶＥＰ）的改变特征。方法 采用电生理方法记录早期原发性开角型青光眼（ＰＯＡＧ）患者在白／黑、红／黑、蓝／黑翻转图形刺激下的ＣＰ－ＥＲＧ、ＣＰ－ＶＥＰ,结果 （１）ＰＯＡＧ组ＣＰ－ＥＲＧ的ｂ波幅值下降,潜伏期延长;ＣＰ－ＶＥＰ的Ｐ１００波幅值下降,潜伏期延长;（２）ＰＯＡＧ组ＣＰ－ＥＲＧ和ＣＰ－ＶＥＰ的异     

Immunofluorescent staining and corneal sensitivity in patients suspected of having herpes simplex keratitis.

We examined immunofluorescent staining and corneal sensitivity in 25 control subjects (25 eyes) with normal corneas, six patients (eight eyes) with possible herpes simplex keratitis, and 44 patients (48 eyes) with corneal lesions (recurrent erosion, superficial punctate keratitis, marginal ulcer, and follicular keratoconjunctivitis) in whom herpes simplex keratitis was not suspected. On immunofluorescent staining, all 25 control subjects had negative reactions, all eight eyes suspected of having herpes simplex keratitis had positive reactions, and 11 (23%) of the 48 eyes not suspected of having herpes simplex keratitis had positive reactions; the remaining 37 eyes had negative reactions. Of the 11 eyes not suspected of having herpes simplex keratitis but that had positive reactions on immunofluorescent staining, nine had recurrent erosions and the remaining two eyes had superficial punctate keratitis. Of the eight eyes with possible herpes simplex keratitis, seven (88%) had decreased corneal sensitivity. Of the 11 eyes not suspected of having herpes simplex keratitis but that had positive reactions on immunofluorescent staining, eight (73%) had decreased corneal sensitivity. Of the 37 eyes not suspected of having herpes simplex keratitis that had negative reactions on immunofluorescent staining, 11 (30%) had decreased corneal sensitivity.     

Drug-induced cicatricial pemphigoid affecting the conjunctiva. Light and electron microscopic features

Cicatricial pemphigoid (CP) is a chronic inflammatory disease which can affect the conjunctiva. It is a slowly progressive disorder of unknown but presumed autoimmune etiology. Pseudopemphigoid, or CP associated with ocular drug administration, has also been described. These cases, which appear clinically indistinguishable from unilateral idiopathic CP affecting the conjunctiva, have been related to the use of echothiophate iodide, pilocarpine, idoxuridine, and epinephrine. We report the histopathologic and ultrastructural characteristics of 22 biopsies from ten patients with iatrogenic CP following the use of various ocular drugs. All patients presented with clinically obvious, active CP affecting the conjunctiva. Light microscopy and electron microscopy revealed findings identical to those previously reported for idiopathic CP of the conjunctiva: squamous metaplasia, increased numbers of desmosomes, basal lamina modifications suggestive of damage and attempted repair, subepithelial inflammatory cell infiltration, and diminished intravascular space within the stroma. These patients responded to immunosuppressive therapy. The authors wonder if it is possible that these patients were destined to develop CP, but that with topical ocular drug use, a more rapid emergence of the chronic cicatrizing feature of CP developed.     

Serologic tests in the diagnosis of presumed toxoplasmic retinochoroiditis

We treated three patients who had documented Toxoplasma retinochoroiditis and negative immunofluorescent antibody toxoplasmosis titers (titer less than 1:16), positive Sabin-Feldman dye titers of 1:64, 1:16, and 1:64 in the three patients, respectively, and a positive enzyme-linked immunoassay titer of 1:256 in the one patient tested. In patients with negative immunofluorescent antibody toxoplasmosis titers, we recommend obtaining Sabin-Feldman or enzyme-linked immunoassay titers, or both, before excluding the diagnosis of ocular toxoplasmosis.     

Mucous membrane pemphigoid and pseudopemphigoid

PURPOSE: To describe the clinical characteristics of patients with mucous membrane pemphigoid (MMP) and pseudopemphigoid. DESIGN: Retrospective cohort study. PARTICIPANTS: Two hundred eighty consecutive patients referred for the evaluation of possible ocular MMP from January 1, 1985, to December 31, 2001. METHODS: Information on patients presenting for evaluation of possible MMP was entered prospectively into a database, which was supplemented by a retrospective chart review. Mucous membrane pemphigoid was diagnosed in patients with a compatible clinical picture by the linear deposition of antibodies to the basement membrane zone (BMZ) on direct immunofluorescent analysis of a mucous membrane biopsy specimen or by the presence of circulating autoantibodies to epithelial BMZ. MAIN OUTCOME MEASURES: Demographic and clinical characteristics of MMP and pseudopemphigoid; risk of ocular MMP among patients presenting with extraocular MMP without ocular disease. RESULTS: Among patients with ocular MMP, extraocular disease was common (82.4% of patients). The risk of ocular involvement among patients with MMP seen without ocular disease was approximately 5% per year over the first 5 years of follow-up (cumulative risk at 5 years, 22%). Although immunohistologic confirmation of the diagnosis was obtained in all patients, the initial conjunctival biopsy was positive for MMP in 80% of the patients diagnosed with ocular MMP. The most frequent presumed causes of pseudopemphigoid were topical glaucoma medications (28.3%), rosacea blepharoconjunctivitis (20.0%), atopic keratoconjunctivitis (8.3%), and conjunctival lichen planus (8.3%). CONCLUSIONS: Patients with ocular MMP typically have other systemic manifestations of MMP. Patients who are initially seen with extraocular MMP without ocular involvement are at risk for ocular disease developing. The clinical characteristics of ocular MMP and pseudopemphigoid are similar; therefore, immunohistologic evaluation of biopsied tissue is needed to confirm the diagnosis of MMP.     

A systematic approach to the diagnosis and treatment of chronic conjunctivitis

In 58 patients with chronic conjunctivitis of greater than two weeks' duration, examination included obtaining an ocular and general medical history and performing a complete ophthalmic examination of the external eye. Conjunctival smears were obtained for Gram and Giemsa staining, direct immunofluorescent monoclonal antibody staining for Chlamydia trachomatis and herpes simplex virus, and chlamydial culture. Cultures for bacteria and viruses were obtained in 33 patients. The cause of the chronic conjunctivitis based on clinical and laboratory criteria was established in 40 of 58 (69%) patients: chlamydia, 11 (19%); virus, eight (14%); irritant, six (10%); allergen, four (7%); contact lens, four (7%); bacteria, four (7%); acne rosacea, two (3%); and floppy eyelid syndrome, one (2%). In 18 of 58 (31%) patients, no specific cause was detected. We recommend a systematic approach in the investigation of chronic conjunctivitis. Direct immunofluorescent monoclonal antibody staining is an effective and rapid technique for detecting chronic chlamydial conjunctivitis.     

A point prevalence study of 150 patients with idiopathic retinal vasculitis: 2. Clinical relevance of antiretinal autoimmunity and circulating immune complexes.

This study describes the occurrence of antiretinal antibodies and circulating immune complexes in the sera of a large series of patients with idiopathic retinal vasculitis whose ophthalmological and clinical features are presented in Part 1. Antiretinal antibodies were measured by indirect immunofluorescence and passive haemagglutination, and circulating immune complexes were measured by polyethylene glycol precipitation and Clq binding. The occurrence of antiretinal antibodies and that of circulating immune complexes were analysed in relation to each other, to severity of retinal disease, to the type of associated systemic inflammatory disease, and to the presence of individual features of retinal inflammation. In patients with retinal vasculitis together with systemic inflammatory disease circulating immune complexes were usually accompanied by antiretinal antibodies. However, those patients with antiretinal antibodies in the absence of circulating immune complexes tended to have more severe retinal vasculitis, a feature particularly evident in Behçet''s disease (p = 0.028). In patients with isolated retinal vasculitis, severity of disease was associated with antiretinal antibody (p = 0.013), as well as with the occurrence of both antiretinal antibody and circulating immune complexes together (p = 0.010). In the series as a whole there was a tendency for individual features of retinal vasculitis to be associated with antiretinal antibodies unaccompanied by circulating immune complexes; especially in macular oedema (p = 0.028). In isolated retinal vasculitis there was also an additive effect of antiretinal antibodies and circulating immune complexes in relation to disease severity; in contrast, in patients with systemic inflammatory disease, the coexistence of antiretinal antibodies and concluded that both antiretinal autoimmunity and circulating immune complexes may act as immunopathogenetic factors in idiopathic retinal vasculitis but that, in certain patients, circulating immune complex formation seems to protect against the more severe forms of autoimmune retinal inflammatory disease.     

Latent oculogenital infection with Chlamydia trachomatis

Thirty patients attending a sexually transmitted disease clinic were evaluated for genital and ocular infection with chlamydia. Eight patients had positive conjunctival immunofluorescent staining. This represents an asymptomatic, latent carrier state with important epidemiologic considerations.     

Indirect immunofluorescent antibody diagnosis of herpes simplex with upper tarsal and corneal scrapings

Indirect immunofluorescent techniques were used to diagnose active herpes simplex virus ocular infections in 84 patient observations (41 with ocular lesions suspicious clinically for herpes simplex and 43 with lesions suspicious clinically for other ocular inflammatory conditions). We found indirect immunofluorescent antibody techniques to have a high sensitivity (97%) and specificity (73%) when compared to herpes simplex virus cultures. Similarly, we found the sensitivity (98%) and specificity (77%) of indirect immunofluorescent antibody techniques to be high when compared to the clinical diagnosis of herpes simplex viral infection. Significantly, there were no false negative tests by indirect immunofluorescent techniques. Both corneal and upper tarsal scrapings by indirect immunofluorescence were used and the upper tarsal scrapings were an excellent source of cells exhibiting herpes simplex virus antigens. All cases in which corneal scrapings were positive by indirect immunofluorescence for herpes simplex ere also positive by upper tarsal scrapings, although the converse was not true.     

SDS-gradient polyacrylamide gel electrophoresis of individual ocular mucus samples from patients with normal and diseased conjunctiva

Individual mucus samples were collected from normal individuals and from patients with ocular cicatricial pemphigoid (CP), Stevens-Johnson syndrome (SJS), and various types of conjunctival inflammation (rosacea, meibomianitis, atopy, keratoconjunctivitis sicca, etc.). The mucus samples were dissolved in sample buffer containing 8M urea, 2% SDS and 5% 2-mercaptoethanol and were electrophoresed on gradient 2-16% polyacrylamide gels. Four glycoproteins with molecular weights greater than 200,000 daltons were consistently observed in both individuals with normal conjunctiva and patients with CP, SJS, and other diseases exhibiting conjunctival inflammation. The amounts of each glycoprotein appeared to vary from one individual to another; however, the presence or absence of specific glycoproteins could not be correlated with the different ocular diseases. The techniques described for mucus analysis offer advantages over previously published techniques since improved resolution of the mucous glycoproteins can be achieved by electrophoresis on 2-16% gradient gels, and individual samples can be analyzed. Our results suggest that substantial amounts of ocular mucous glycoprotein are present in the eyes of patients with CP and SJS, diseases which have been previously described as mucin-deficient dry eye syndromes.     

Circulating hematopoietic stem cells in patients with idiopathic choroidal neovascularization

PURPOSE: In a prior study, the correlation was investigated between circulating hematopoietic stem cells (HSCs) and the activity or severity of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). The present study was designed to explore the role of circulating HSCs in the pathogenesis of CNV in patients with idiopathic (i)CNV. METHODS: Thirteen patients with clinically documented iCNV and 10 age-sex matched patients without iCNV or systemic disease were enrolled in a case-control study. Circulating HSCs were collected from the patients' peripheral blood and cultured. Colony-forming capacity, migration activity, and invasion activity of HSCs were experimentally analyzed. RESULTS: Colony-forming units by Hill's assay (CFU-Hill) were markedly lower (P<0.001) in patients with iCNV (12.8+/-3.2) than in healthy patients (67.6+/-12.6). Invasion activities of HSCs were reduced significantly in patients with iCNV. CFU-Hill was impaired in the patients (4.0+/-1.2) with CNV more than 1500 microm compared with the patients (20.3+/-4.0) with CNV less than 1500 microm (P=0.006). CONCLUSIONS: Similar to the previous finding of CNV associated with AMD, impaired functional activities of circulating HSCs were observed in patients with iCNV, which correlated with the size of iCNV. These results in young patients provide evidence to support the role of circulating HSCs in the pathogenesis of CNV.     

Differences in energy and corneal endothelium between femtosecond laser-assisted and conventional cataract surgeries: prospective, intraindividual, randomized controlled trial

AIM: To compare intraoperative phacoemulsification parameters and its effect on the corneal endothelium of eyes undergoing femtosecond laser-assisted cataract surgery (FLACS) versus conventional phacoemulsification (CP) cataract surgery. METHODS: Two hundred eyes from one hundred patients were included in a prospective, non-blinded, randomized, controlled, intraindividual clinical study. One hundred eyes underwent FLACS while their one hundred fellow eyes underwent CP. All surgeries were performed using the Victus® femtosecond laser platform and Infinity® Vision System phacoemulsification machine. Primary outcome measure was endothelial cell density 6mo after surgery. Secondary outcome measures included central corneal thickness (CCT), average cell area, standard deviation, coefficient of variation and hexagonality before surgery and 6mo after surgery and endothelial cell density loss during this period were also evaluated. Intraoperative efficiency parameters [cumulative dissipated energy (CDE), total intraocular surgery time, total ultrasound time, total phacoemulsification time, total torsional energy time, total aspiration time, ultrasound energy, torsional amplitude and fluid required during surgery] were also collated. RESULTS: Data from these patients was not considered for analysis. Data from 92 patients were analysed. Postoperative endothelial cell density (cells/mm2) between groups (2211.88±392.49 CP; 2246.31±403.48 FLACS) was not statistically significant (P=0.869). Total ultrasound time, torsional energy time, CDE and fluid requirements were significantly lower the FLACS group (P<0.05). Other parameters did not show statistically significant difference between FLACS and CP. CONCLUSION: FLACS displays significant improvements in phacoemulsification parameters in comparison to CP. There are no significant differences in corneal endothelium measures between FLACS and CP.     

角膜穿孔临床研究分析

目的：研究角膜穿孔(corneal perforation,CP)患者的临床发病特点。

方法：回顾性分析1995-07/2010-07福建医科大学附属第一医院住院确诊的CP患者72例72眼,分析其患者临床特点。

结果：福建地区角膜溃疡穿孔发病率逐年上升,男女发病率比为 17：7 , 48岁为发病集中年龄,产业工人 23例(32%),23例有明确外伤史,菌属鉴定结果：前两位为：真菌感染和棘阿米巴原虫感染。 其中10例有糖皮质激素用药史。

结论：外伤、真菌性、棘阿米巴角膜炎、蚕食性角膜炎等所致CP的原发病因多种多样,福建地区CP多发于中老年的男性,多数外伤为诱因,致病菌属以真菌感染为主。     

Ocular defects in cerebral palsy

There is a high prevalence of ocular defects in children with developmental disabilities. This study evaluated visual disability in a group of 200 cerebral palsy (CP) patients and found that 68% of the children had significant visual morbidity. These findings emphasize the need for an early ocular examination in patients with CP.     

Ocular alignment and results of strabismus surgery in neurologically impaired children

AIM: To evaluate ocular alignment and surgical results of strabismus surgery in neurologically impaired children. METHODS: Files of 33 neurologically impaired squint children were evaluated. Twelve patients had cerebral palsy(CP), 4 had CP with mental retardation, therest had mental-motor retardation of unknown cause. Cycloplegic refractions, type and angle of strabismus, surgeries performed were recorded. RESULTS: Mean follow-up was 34.0±16.5 months. Twenty-three patients had esodeviation, the remaining had exodeviation. In 19 patients, angle of deviations measured at different visits were highly variable. Twelve patients with stable angle of deviations or with unstable but high angle deviations had horizontal muscle surgery. Mean horizontal deviation decreased from 43.75±10,69 D to 12.83±8.38 D with surgery. CONCLUSION: In neurologically impaired strabismic children, surgery is effective in patients with stable deviations or unstable but high angle deviations. Decision for surgery should be made after a long follow up period.