Primary local orbital amyloidosis: biochemical identification of the immunoglobulin light chain kappaIII subtype in a small formalin fixed, paraffin wax embedded tissue sample.

BACKGROUND: Amyloidosis refers to a heterogeneous group of disorders associated with the deposition of chemically distinct amyloid fibril proteins. Precise determination of chemical amyloid type has diagnostic, therapeutic, and prognostic relevance. Although immunohistochemical techniques are used routinely to determine the amyloid type, the results can be negative or inconclusive, so that biochemical characterisation is often required. The development and application of new biochemical microtechniques suitable for examination of extremely small tissue samples is essential for precise identification of the deposited amyloid proteins. AIMS: To investigate biochemically the amyloid proteins present in a formalin fixed paraffin wax embedded orbital tissue from a patient with localised orbital amyloidosis in whom immunohistochemistry was not helpful in the determination of amyloid type. METHODS: Extraction of amyloid proteins from fixed tissue and their identification was carried out by a recently developed microtechnique. An extremely small tissue sample was dewaxed and extracted with formic acid. The extracted material was analysed using electrophoresis, western blotting, and amino acid sequencing. RESULTS: Biochemical examination of the extracted proteins showed the presence of immunoglobulin (Ig) derived amyloid proteins, which were composed of the N-terminal fragments of the Ig light chain kappaIII subtype (AL-kappaIII) (16, 8, and 3 kDa). CONCLUSIONS: This is the first chemically proved AL case reported in association with primary localised orbital amyloidosis. The biochemical microtechnique used was useful in achieving a precise diagnosis of amyloid disease, in a case where the results of routine immunohistochemical examination of amyloid were inconclusive.

Metoprolol responding uveitis.

BACKGROUND: Noninfectious uveitis is usually managed by topical and systemic corticosteroids and in refractory cases by immunosuppressive drugs. OBJECTIVE: To describe a patient with noninfectious anterior and posterior uveitis, refractory to corticosteroids, and immunosuppressive therapy, which responded to systemic metoprolol. PATIENT AND METHODS: A 49-year-old patient was treated for 3 years with topical and systemic corticosteroids and systemic cyclosporin A for a bilateral anterior and posterior uveitis of unknown origin. The treatment did not result in resolution of the uveitis. A bilateral uveitic glaucoma developed and necessitated neodymium : YAG laser iridotomies and antiglaucoma medications. A systemic beta-blocker, metoprolol tartrate 50 mg b.i.d., was administered for palpitations because of idiopatic paroxysmal supraventricular tachycardia and short ventricular tachycardia. RESULTS: Following administration of metoprolol tartrate, the bilateral uveitis resolved. The corticosteroids and the cyclosporin A were withdrawn after 6 weeks without any recurrence. A trial to discontinue metoprolol after 6 months resulted in flare-up of the disease and only following its readministration the inflammation resolved. The patient is currently under metoprolol for a year without flare-ups. CONCLUSIONS: The use of metoprolol tartrate in this patient resulted in resolution of bilateral noninfectious uveitis. This is the first report of non-antiinfectious, antiinflammatory, or immunosuppressive drug effective for uveitis. It is possible that a subgroup of resistant uveitis may respond to drugs other than the traditional drugs, such as metoprolol, and that other forms of uveitis of unidentified origin exist.

Correlation between optic disc atrophy and aetiology: anterior ischaemic optic neuropathy vs optic neuritis.

BACKGROUND: The morphologic features of swollen disc in the acute stage of optic neuritis and anterior ischaemic optic neuropathy (AION) have been extensively investigated in contrast to the morphologic features of optic disc atrophy after these events. OBJECTIVE: : A prospective study to evaluate the morphologic features of optic disc atrophy 6 months or more after optic neuritis and nonarteritic AION. PATIENTS AND METHODS: A total of 35 optic discs after nonarteritic AION (n=27) and 24 after optic neuritis (n=19) in otherwise healthy subjects have been evaluated by direct fundoscopic examination with a +90 diopters lens and optic disc photography. The average age of patients at the onset of AION was 57.8 years (range: 38-80) and at the onset of optic neuritis was 32.6 (range: 19-46). The female:male ratio was 18 : 17 in the former and 15 : 9 in the latter. The evaluated parameters included: degree of rim pallor (0 to +3), location of rim pallor, height of rim above the retina, depth and width of cup, peripapillary retinal artery to vein (A : V) ratio, and peripapillary pigment epithelial atrophy. A comparison was made also with 17 age-matched normal discs of 17 patients. Statistical significance was calculated with chi(2) and Fisher's exact test. RESULTS: Most of the discs after AION were paler (+2: 70%, +3: 26%) than after optic neuritis (normal colour: 8%, +1: 58%, P< or =0.007). Rim segmental involvement after AION was usually either superior 'altitudinal' (53%) or inferior 'altitudinal' (29%), whereas after optic neuritis, it was usually either temporal-central (papillomacular) (42%) or diffuse temporal (42%, P<0.0001). Discs had lower A : V ratio (1 : 3, 40%) after AION compared with optic neuritis (1 : 3, 8%) (P=0.007). There were no significant differences between the two groups in height of the rim, cupping, and peripapillary atrophy. CONCLUSIONS: : A combination of the degree of rim pallor, location of rim pallor, and A : V ratio may be of value in assessing the aetiology of optic disc atrophy when no previous clinical data are available and a compressive lesion has been ruled out.

Development and progression of cataract in patients required repeated corneal transplantation.

PURPOSE: To evaluate the incidence of cataract development in patients required repeated corneal transplantations, the types of cataract and the effect of cataract extraction on the corneal regrafts survival. PATIENTS AND METHODS: The charts of all the patients that underwent repeated corneal transplantation between 1985 and 1998 were reviewed for the development of cataract after the first or subsequent keratoplasties. In all, 80 patients underwent 122 repeated corneal transplantations, of which six underwent surgery in both eyes. The average follow-up period of all the patients with repeated keratoplasty was 89.5 months from the first keratoplasty. RESULTS: Of 86 eyes 19 (22%) that underwent repeated keratoplasties developed cataract. The cataract developed between 1 month and 17 years (average 61.3 months) after the first transplantation. The incidence of cataract development was independent of the number of repeated keratoplasties. In certain patients, such as patients with acute and severe regraft immune rejection, the cataract progressed more rapidly. Despite different cataract extraction procedures, the grafts in 17 eyes of the 19 (89.5%) failed following cataract surgery and 16 of them underwent additional corneal regrafting. The regrafts in eight of the 16 regrafted eyes (50%) remained clear with improvement in visual acuity. At the end of the follow-up, 10 eyes of the 19 had clear regraft (53%) comparable with the rate of clear grafts in the entire regrafted group (51%, P=NS). CONCLUSION: Corneal transplantation may be a trigger for slow development of cataract over years but repeated keratoplasties did not increase the risk for cataract development. Although failure of regrafts may occur after cataract extraction, subsequent corneal transplantation has a comparable survival and visual outcome with the entire regrafted group.

Systemic cyclosporin A in high failure risk, repeated corneal transplantation.

AIM: To evaluate the efficacy of oral cyclosporin A in the prevention and treatment of immune graft rejection in heavily vascularised, repeated keratoplasties with high risk for failure. METHODS: 21 consecutive patients with 28 repeated corneal transplants and four quadrant vascularised recipient bed were treated with oral cyclosporin A for an average period of 12 months (range 1-41 months) and followed for an average period of 26.6 months (range 6-106 months). The average cyclosporin A blood level was 325 ng/ml (range 180-421 ng/ml). Within this group of 21 patients, another 12 regrafts were not treated with cyclosporin A and served as a control group. RESULTS: Nine of the 28 regrafts (32%) treated with cyclosporin A remained clear. The Kaplan-Meier curve showed a constant decline in survival of the treated grafts, although the survival proportion during the first year of treatment was statistically higher for the treated group compared with the untreated group. Once immune regraft rejection occurred, the regraft failed despite treatment with cyclosporin A and extensive topical and systemic corticosteroids. Nine regrafts (32%) had immune graft rejection and all ultimately failed compared with five in the untreated regrafts (42%, p = NS). Ten other regrafts (36%) in the treatment group failed due to causes other than immune regraft rejection. CONCLUSIONS: Systemic cyclosporin A has a limited beneficial effect in preventing immune graft rejection in repeated corneal transplants in a highly vascularised corneal bed. When immune graft rejection occurs in such regrafts, the prognosis is poor despite aggressive medical treatment. Causes other than immune regraft rejection may also result in poor visual outcome in patients with clear regrafts.

Ultrastructure of the lamellar corneal wound after laser in situ keratomileusis in human eye.

A 30-year-old patient with keratoconus, a stable refraction, and normal central corneal thickness had laser in situ keratomileusis (LASIK). Six months later, she had uneventful penetrating keratoplasty for keratectasia. The lamellar LASIK interface could not be clearly identified by light microscopy. The corneal wound site did not stain for methyl metalloproteinase 1 or 2. Both the corneal flap undersurface and the stromal bed were devoid of interconnections and cells. Throughout the lamellar incision, including the laser-ablated zone, the surface was smooth on scanning electron microscopy. The collagen fibrils on both sides of the incision remained well aligned with one another, indicating good flap apposition. Under higher magnification transmission electron microscopy, some collagen fragments were found in the interface, especially adjacent to the hinge. The diameter of the collagen fibrils along the lamellar wound were identical to those farther from the incision. The absence of bridging collagen fibrils and cells between the flap undersurface and the stromal bed confirms the clinically known lack of wound repair at the interface and explains the easy separation of the flap from the stromal bed months after LASIK and the possible formation of an interface fluid pocket.

The profile of repeated corneal transplantation.

PURPOSE: To evaluate the primary indications for corneal transplantation in patients with repeated keratoplasties, graft survival, the causes and risk factors for failure. SETTING: Tertiary referral care center. DESIGN: Retrospective, noncomparative case series. METHODS: Charts of all patients who underwent repeated corneal transplantation between 1985 and 1998 were reviewed. Eighty patients underwent repeated corneal transplantation, of which six underwent repeated corneal transplantation in both eyes, totaling 86 eyes. A total of 208 keratoplasties were performed in this group; 86 primary and 122 repeated keratoplasties. The most common primary indications for corneal transplantation were vascularized corneal scar in 31 of the 86 eyes (36%), followed by pseudophakic and aphakic bullous keratopathy (PBK, ABK). Of the repeated transplants, 55 eyes (64%) had one repeated graft, 27 eyes (31.4%) had two repeated grafts, three (3.5%) had three repeated grafts, and one (1.2%) had four repeated transplants. MAIN OUTCOME MEASURES: Final visual outcome and clarity of corneal graft. RESULTS: At the end of the follow-up period, 44 of the 86 eyes (51%) had clear grafts, but only 39.5% had good visual outcome. The mean survival periods of the repeated transplants decreased gradually with the number of regrafting procedures, from 14.3 to 8.7 months. The mean survival period was longer for patients with ABK, PBK, and secondary glaucoma, and shorter for patients who experienced graft ulcer or surface disorders. Graft failure was unrelated to graft size, but was associated with vascularization (P = 0.025), additional surgical procedures (P < 0.0001), and postoperative complications (P < 0.0001). There was a constant tendency for decrease in visual acuity with time. Final visual acuity was 20/20 to 20/40 in 13 of the 86 eyes (15%), 20/80 to 20/200 in 23 eyes (27%), and less than 20/200 in 50 eyes (58%). The most common complication was immune rejection, which occurred in 65 of the 208 transplants (31%), followed by secondary glaucoma in 48 eyes (23%) and cataract in 19 eyes (9%). Graft survival decreased remarkably after the third and forth regrafts, to 25% and 0%, respectively, compared with the first and second regrafts, 37% and 43%, respectively. CONCLUSIONS: "High-risk" preoperative conditions, postoperative complications, and the need for additional surgical interventions may decrease graft survival. Close follow-up, extended use of antiinflammatory, antiviral, and immunosuppressive drugs, and avoiding additional surgical interventions as much as possible may decrease graft failure and the need for repeated keratoplasties.

Corneal co-infection with Scedosporium apiospermum and Acanthamoeba after sewage-contaminated ocular injury.

PURPOSE: To describe a corneal co-infection with the fungus Scedosporium apiospermum and Acanthamoeba that result in spontaneous corneal perforation. METHODS: A 27-year-old man presented due to severe ocular pain in his left eye caused by a corneal ulcer. The patient was injured 7 days before presentation by metallic thread contaminated by sewage. Corneal scrapping and deep stromal biopsy were obtained and stained for microscopic evaluation with periodic acid-Schiff, Giemsa, and Gomori's methenamine silver stains. Samples were sent for aerobic and anaerobic bacterial and fungal cultures. RESULTS: Corneal biopsy and corneal scrapping showed viable Acanthamoeba cysts in the corneal stroma and S. apiospermum micelle, respectively. The fungal culture was sensitive to ketoconazole, miconazole, econasole, and traconazole. Devastating corneal perforation occurred despite aggressive antifungal and antiamoebic topical and systemic treatment initiated after diagnosis. The corneal button showed a necrotic tissue devoid of inflammatory cells and microorganisms. CONCLUSION: S. apiospermum and Acanthamoeba may co-infect immune privilege sites, such as the cornea, in immunocompetent hosts. Compromised corneal surface, e.g., after trauma by sewage-contaminated objects, may increase the susceptibility for such devastating coinfection. Prevention may be possible by use of protective eyewear by high-risk individuals. Treatment should be initiated promptly with broad-spectrum antimicrobial agents after ocular injury by sewage-contaminated objects. Repeated corneal cultures and biopsies, if the cultures are negative, are warranted. Corticosteroids should be withheld until the causative agents are identified and targeted treatment is initiated.

Marginal corneal infiltrates: a possible new manifestation of sinus histiocytosis with massive lymphadenopathy.

PURPOSE: To describe unilateral deep marginal corneal infiltrates and chronic anterior uveitis in a young patient with sinus histiocytosis and massive lymphadenopathy. METHODS: A 20-year-old man with a painless enlargement of his cervical lymph nodes was followed for five years after debulking of these nodes on the right side for right chronic anterior uveitis and deep marginal corneal infiltrates. RESULTS: Histological sections of cervical lymph node confirmed the diagnosis of sinus histiocytosis with the typical emperipolesis. The uveitis partially responded to topical corticosteroid treatment but tended to recur upon its withdrawal. The marginal corneal infiltrates resolved gradually over a period of five years. CONCLUSIONS: Marginal corneal infiltrates and uveitis may presumably be associated with sinus histiocytosis. Patients with sinus histiocytosis should also be screened for rare ocular involvement, such as uveitis and corneal infiltrates.

Ultrastructural changes in corneas of diabetic patients: an electron-microscopy study.

BACKGROUND: Although diabetic retinopathy has been thoroughly studied, little attention has been given to the corneal changes of diabetic patients. Pathophysiologic and clinical findings may be related to the ultrastructural changes found in these corneas. PURPOSE: To investigate the ultrastructural corneal changes of diabetic patients. PATIENTS AND METHODS: Transmission electron microscopic ultrathin sections were prepared from corneas of 16 noninsulin-dependent diabetic patients (mean age, 65 years; range, 40-82 years) who suffered from the disease for a mean period of 22 years (range, 10-30 years). We used 16 corneas from healthy age-matched donors as normal controls. RESULTS: In addition to the epithelial changes that include accumulation of glycogen granules, occasional focal epithelial cell degeneration, and irregular thickening and multilamination of the epithelial basement membrane, unusual 120-nm wide-spaced collagen fibril bundles were observed scattered among both Descemet's membrane and stromal matrix. CONCLUSIONS: The aggregates of wide-spaced collagen fibrils, which have not been described in other basement membranes of diabetic patients, may reflect an excessive glycosylation rate.

Collagen pleomorphism in Descemet's membrane of streptozotocin-induced diabetic rats: an electron microscopy study.

BACKGROUND: Diabetes mellitus causes ultrastructural changes in various basement membranes. These changes include increase in collagen biosynthesis rate and production of altered collagen. PURPOSE: To evaluate the ultrastructural changes in the corneas of streptozotocin- induced diabetic rats, focusing on Descemet's membrane. METHODS: Sprague-Dawley rats were sacrificed at different intervals after induction of diabetes mellitus by streptozotocin. Ten animals were sacrificed 1, 2, 3, 4, 6, 8, and 12 months after the injection of streptozotocin. Five untreated rats of the same age were used as normal controls and were sacrificed at the same intervals. Ultrathin sections were obtained from the corneas and were examined by transmission electron microscopy. RESULTS: Unusual 120-nm-spaced collagen fibril bundles were found in Descemet's membrane of the diabetic rats as early as the second month following the induction of diabetes. Their concentration and size increased gradually over the follow-up period of 12 months. CONCLUSIONS: Changes in the morphologic features of the collagen within Descemet's membrane may occur in diabetic-induced rats. The appearance of wide-spaced collagen fibrils in Decemet's membrane may represent alteration in collagen biosynthesis by the endothelial cells in diabetes or altered assembly of collagen due to increased glycosylation of normal formed collagen.

Paradoxical hypotony after laser in situ keratomileusis.

We present a case of paradoxically low (0 to 2 mm Hg) intraocular pressure (IOP) measured by Goldmann applanation and Tono-Pen tonometry in an eye with corticosteroid-induced high IOP after laser in situ keratomileusis. The patient complained of blurred vision and ocular pain in both eyes. The eyes were firm by palpation, and the IOP measured by Schiotz indentation tonometry was 38 mm Hg. An interface fluid pocket was identified by slitlamp examination, and the corneal surface became steeper. These findings resolved after flap relifting, interface irrigation, and addition of antiglaucoma medications. We postulate that the paradoxically low reading by applanation tonometry was due to fluid accumulation within the flap-bed interface. The applanation tonometry reflected the interface fluid pocket pressure rather than the real high IOP. An exceedingly low IOP should be verified by palpation or by Shiotz indentation tonometry, and interface fluid should be identified.

Measurements for horizontal extraocular muscle surgery from the suture site: outcome and influencing factors.

BACKGROUND: Measurement of recession in strabismus surgery is performed either from the limbus or from the muscle insertion. These measurement methods may result in inaccuracies that may influence the outcome of the procedure. We prospectively evaluated the outcome of recessions measured from the extraocular muscle suture site to its insertion in an incidence cohort. METHODS: Thirty-six consecutive surgical procedures for infantile esotropia and 23 for constant exotropia were performed in which measurements were performed from the suture site. A successful surgery for esotropia was defined as an orthophoria of up to +10 prism dioptres of deviation for non-accommodative targets at a distance of 20 feet, measured by cover and prism test. A successful surgery for exotropia was defined as a residual deviation between -10 and +10 prism dioptres. The statistical significance of the outcome influencing factors was assessed by chi-square test. RESULTS: Six weeks following surgery, 28 procedures (78%) for infantile and non-accommodative esotropia and 19 procedures (83%) for exotropia were successful. At the end of the follow-up period (mean 13.7 months +/- 9.4 for esotropia and 11.6 months +/- 12.8 for exotropia), the success rate was 77% for esotropia and 75% for exotropia. Prematurity and mental retardation in esotropia, exotropia with pre-operative deviations larger than -45 prism dioptres and amblyopia in exotropia were related to unfavourable outcome (p < 0.05). CONCLUSIONS: Measurement for muscle recession can be performed from the suture site. The outcome is comparable to the outcome when measurements are performed from the limbus or the insertion, probably due to the incidence cohort. Refinement of the technique and defining other factors influencing the outcome of strabismus surgery may improve the outcome.

Aggressive systematic treatment for central retinal artery occlusion.

PURPOSE: To report the efficacy of an aggressive systematic regimen for the treatment of acute nonarteritic central retinal artery occlusion (CRAO). METHODS: Eleven patients who had unilateral CRAO with symptoms of fewer than 48 hours' duration were treated with an aggressive stepwise systematic regimen until retinal circulation improved or until all the treatment steps were performed. Five patients with unilateral CRAO and symptoms of fewer than 48 hours' duration were treated in the same institution in an arbitrary nonsystematic manner. The therapeutic steps of the aggressive treatment included ocular massage, sublingual isosorbide dinitrate, intravenous acetazolamide, intravenous mannitol or oral glycerol, anterior chamber paracentesis, intravenous methylprednisolone followed by streptokinase, and retrobulbar tolazoline. After each step, retinal flow was evaluated by three-mirror contact lens. The nonsystematic treatment was arbitrary and included one or several of the above. Visual acuity and complete eye examination data were recorded before and after treatment. RESULTS: Visual acuity and retinal arterial supply were improved in eight (73%) of the 11 patients treated in the stepwise systematic manner. All eight patients in whom visual acuity improved had symptoms for fewer than 12 hours, and the presumed cause was either platelet-derived or cholesterol embolus from atheroma or the patients had glaucoma. Patients in whom visual acuity did not improve had CRAO that was attributed to calcified emboli or primary antiphospholipid antibody syndrome and had symptoms more than 12 hours before treatment. Visual acuity did not improve in all five patients with the nonsystematic treatment regardless of the presumed cause or duration of the occlusion. The success of the treatment in the systematic treatment group was statistically significantly better compared with the outcome of the nonsystematic treated group (Fischer exact test, P = .01). CONCLUSIONS: In the treatment of CRAO, an aggressive systematic regimen including medical and mechanical means may reestablish retinal circulation and improve visual outcome. The cause of arterial occlusion, the nature of occlusive emboli, and the duration of retinal ischemia may determine the visual outcome, but a larger series is warranted to verify the effectiveness of the treatment and the prognostic factors.

Diagnosis of chlamydial infection by direct enzyme-linked immunoassay and polymerase chain reaction in patients with acute follicular conjunctivitis.

BACKGROUND: Acute follicular conjunctivitis is a clinical diagnosis common to multiple etiologies, of which chlamydial infection requires specific antibiotic treatment. PURPOSE: This prospective study was designed to evaluate Chlamydia trachomatis as the cause of acute follicular conjunctivitis by two sensitive tests: direct enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). METHODS: Conjunctival scrapings from patients presented with untreated acute follicular conjunctivitis were examined by ELISA and PCR, and patients were followed up for prolongation of the disease course. RESULTS: All 36 consecutive patients presented with acute follicular conjunctivitis were negative for Chlamydia trachomatis by ELISA and PCR. None of the patients had a prolonged course of more than 4 weeks or required treatment with systemic antibiotics as would be expected from chlamydial infection. CONCLUSIONS: Chlamydia trachomatis was probably not responsible for the acute follicular conjunctivitis in this series, and ELISA and PCR may not be cost effective for evaluation of acute follicular conjunctivitis due to chlamydial infection. Further evaluation of the cost effectiveness of these tests is required in chronic follicular conjunctivitis.