Disorders of sex development: timing of diagnosis and management in a single large tertiary center.

BACKGROUND: We describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center. METHODS: DSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts. RESULTS: Among the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 ± 5.5 years), Klinefelter syndrome (14.5%, 6.8 ± 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P < 0.001). CONCLUSIONS: Our results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients' adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.

Transscleral red laser cyclophotocoagulation for the treatment of therapy-resistant inflammatory glaucoma.

PURPOSE: To evaluate in a retrospective study the long-term usefulness of red 647 nm krypton and 670 nm diode laser for transscleral contact cyclophotocoagulation (CPC) in the treatment of therapy-resistant inflammatory glaucoma. METHODS: The authors treated 48 eyes of 38 consecutive patients (mean age 36.8 years, range 6-81 years) with therapy-resistant inflammatory glaucoma secondary to chronic uveitis (45/48), chronic scleritis (1/48), or combined scleritis with keratouveitis (2/48) using transscleral red 647 nm Krypton or 670 nm Diode laser. All eyes had failed maximum tolerated medical therapy and 19/48 (40%) eyes also previous antiglaucoma surgery. Laser power at the scleral surface was 0.35 to 0.45 W and the application time 10 seconds each. The follow-up was 42.8+/- 40.0 (range 2-145) months. RESULTS: The mean preoperative intraocular pressure (IOP) of 35.6+/-8.1 mmHg fell to 6-21 mmHg level in 75% after one or repeated CPC. Among adult patients this was achieved in 85%, among children in 54%. More than one treatment was needed in 52%. No cases of hypotony, phthisis bulbi, or other devastating complications occurred. CONCLUSIONS: Transscleral CPC using red 647 nm krypton or 670 nm diode laser is an effective and well-tolerated procedure for the treatment of therapy-resistant inflammatory glaucoma in adults. CPC can be considered before incisional antiglaucoma surgery with a shunt or antimetabolites is undertaken.

Exfoliation syndrome as a risk factor for cataract development: five-year follow-up of lens opacities in exfoliation syndrome.

PURPOSE: To ascertain whether the exfoliation syndrome (EXS) is a risk factor for cataract development. SETTING: Helsinki University Eye Hospital, Helsinki, Finland. METHODS: This prospective study examined the development of lens opacities using the Lens Opacity Meter. Visual acuity and refraction were measured in both eyes of 63 nonglaucomatous patients with clinically unilateral EXS. After 5 years, 46 patients were available for follow-up. Case histories of 14 patients were recorded. RESULTS: During the 5 year study, the rate of conversion to bilateral disease was 22% and to exfoliative glaucoma, 30%. At the beginning of the study, the mean lens opacity was 23.5 opacity units (OU) +/- 6.7 (SD) in EXS eyes and 22.9 +/- 7.2 OU in fellow, initially nonexfoliative (NE) eyes; the difference was not significant. After 5 years, the mean opacity was 30.0 +/- 8.8 OU in EXS eyes and 26.9 +/- 8.3 OU in NE eyes (P <.001). In patients who remained unilaterally affected, the EXS eye had a higher opacity value than the NE eyes at the start of the study (23.6 +/- 7.3 OU and 22.7 +/- 7.2 OU, respectively) (P <.05) and after 5 years (29.9 +/- 9.0 OU and 27.0 +/- 8.5 OU) (P <.01). There was a significant myopic change in refraction over time in both groups. The mean refraction in EXS eyes was +1.02 +/- 2.48 diopters (D) at the start and + 0.11 +/- 3.06 D after 5 years (P =.0001) and in NE eyes, +0.99 +/- 2.25 D and +0.43 +/- 2.55 D, respectively (P <.01). At the start of the study, the mean difference in refraction between fellow eyes (refraction in NE eye - refraction in EXS eye) was -0.27 +/- 1.00 D. After 5 years, it was +0.32 +/- 1.44 D (P =.016), showing a greater myopic change in EXS eyes. CONCLUSION: The results show that EXS is a risk factor for lens opacification.

Changes in visual acuity and refraction in the exfoliation syndrome. A five-year follow-up study.

PURPOSE: To examine changes in visual acuity (VA) and refraction in non-glaucomatous patients with unilateral exfoliation syndrome (EXS). METHODS: The best corrected values for VA (Snellen acuity cards) subjectively adjusted for refraction, and IOP were measured, and the development of lens opacities was examined in 46 non-glaucomatous patients with unilateral EXS. RESULTS: After five years the rate of conversion to bilateral exfoliation was 22% and to exfoliative glaucoma 30%. There was a significant decrease in VA in the exfoliative (E) eyes (median; QI, QIII, range: 1; 0.8, 1, 0.4-1.3 vs. 0.55; 0.4, 1, 0.05-1.4, p<0.0001) and the fellow, initially non-exfoliative (NE), eyes (1; 0.9, 1, 0.3-1.3 vs. 0.7; 0.5, 0.9, 0.1-1.4, p<0.0001) and a significant myopic change in refraction in the E eyes (+1.02 +/- 2.48 vs. +0.11 +/- 3.06, p=0.0001) and the NE eyes (+0.99 +/- 2.25 vs. +0.43 +/- 2.55 D, p<0.01). At study entry the difference in refraction between the fellow eyes (refraction in the NE eye--refraction in the E eye) was -0.27 +/- 1.00D. After five years it was +0.32 +/- 1.44 (p 0.016), reflecting greater myopic changes in the E eyes. The main type of lens opacification was nuclear sclerosis. CONCLUSIONS: In five years, significant decreases in VA and myopic shifts in refraction occurred in the E and fellow eyes. The E eyes showed significantly greater myopic changes than the fellow eyes; the cause was clearly nuclear sclerosis, which must be taken into account in the long-term management of patients with EXS.

Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma.

PURPOSE: To investigate the hypothesis that tumor-infiltrating macrophages contribute to prognosis of uveal melanoma and to study their association with tumor characteristics, especially microvessels. METHODS: This was a retrospective, population-based cohort study of 167 consecutive patients who had had an eye with choroidal and ciliary body melanoma removed between 1972 and 1981. Macrophages were identified with mAb PG-M1 to the CD68 epitope, and their number and morphologic type were recorded. Kaplan-Meier and Cox regression analyses of melanoma-specific survival were performed. RESULTS: CD68-positive macrophages could be assessed in 139 (83%) of the 167 melanomas. Their number was moderate to high in 115 (83%) of the 139 tumors, and their morphology ranged from dendritic to round. A high number of macrophages was associated with presence of epithelioid cells (P = 0.025), heavy pigmentation (P = 0.001), and high microvascular density (P = 0.001). The 10-year melanoma-specific mortality rate increased with higher numbers of macrophages (0.10 for low versus 0.57 for high numbers, P = 0.0012). The morphologic type of infiltrating macrophages was not associated with mortality. The number of macrophages was modeled by stratification, which significantly improved a Cox regression model (P < 0.001). Adjusting for the other independent indicators of metastatic death 10-year melanoma-specific mortality was 0.17 for low versus 0.45 for high numbers of macrophages. CONCLUSIONS: The number of tumor-infiltrating CD68-positive macrophages contributes to prognosis and associates with cell type and microvascular density, which merits a further analysis of the biological role of these cells in uveal melanoma.

Corneal pathology and outcome of keratoplasty in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

BACKGROUND: Disabling, chronic, persistent keratoconjunctivitis is an essential ocular manifestation in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). PURPOSE: Because of the paucity of previous studies our aim is to describe the main histopathological features of the keratopathy and to report the long-term outcome of corneal grafting. MATERIAL: Four corneal buttons obtained at keratoplasties. Two patients with clinical follow-up data of 30 years. RESULTS: The corneal epithelium showed a severe atrophy with even areas of incipient epidermalization. The Bowman's membrane was destroyed. The anterior corneal stroma was replaced by vascularized scar tissue with areas of chronic inflammatory cell infiltration consisting mainly of lymphocytes and plasma cells. The posterior corneal stroma, the Descemet's membrane and the endothelium were normal. Rejection occurred after each keratoplasty. The last visual acuity of the first patient was finger counting of the right eye and 0.3 of the left eye and of the second patient 0.08 of both eyes. CONCLUSION: In chronic keratopathy of APECED the anterior corneal layers, the epithelium, the Bowman's membrane and the anterior corneal stroma are affected while the posterior cornea appears normal. As after keratoplasty rejection may be expected, its prevention and management need intensive attention.

Corneal morphology and sensitivity in lattice dystrophy type II (familial amyloidosis, Finnish type).

PURPOSE: To describe the corneal abnormalities and to measure different modalities of corneal sensitivity in corneal lattice dystrophy type II (familial amyloidosis, Finnish type, also known as gelsolin-related amyloidosis and originally as Meretoja syndrome). METHODS: Twenty eyes of 20 patients were examined by in vivo confocal microscopy and noncontact gas esthesiometry. RESULTS: Pleomorphism of, and dense deposits between or posterior to, the basal epithelial cells were frequently observed, as well as a reduction of long nerve fiber bundles in the subbasal nerve plexus. The anterior stroma was altered in most cases, with fibrosis and abnormal extracellular matrix. In 15 corneas, thick anterior and midstromal filaments, corresponding to lattice lines, and in 11 corneas, thin undulated structures were observed. The average mechanical sensitivity threshold of 12 subjects was increased, and in the remaining 8 subjects there was no response, even to the highest intensity of stimuli used. Three patients did not respond to CO(2), 11 to heat, and 2 to cold, but those patients who responded had normal thresholds. Patients with more long nerve fiber bundles per confocal microscopic image had better mechanical and cold sensitivity than patients with fewer nerve fiber bundles. CONCLUSIONS: Lattice lines seem to be related to amyloid material and not to corneal nerves. However, the subbasal nerve density appears reduced, which results mainly in a decrease in mechanical and, to a lesser extent, thermal sensitivity. The location of stromal filaments and undulated structures changes with increasing age.

Chronic bilateral keratitis in autoimmune polyendocrinopathy-candidiadis-ectodermal dystrophy (APECED). A long-term follow-up and visual prognosis.

PURPOSE: To report the outcome of chronic bilateral keratitis and other ocular manifestations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). MATERIAL AND METHODS: The material consists of 69 patients with APECED, who were examined by the senior author as referrals from the pediatricians. The patients were seen at the Helsinki University Eye Hospital a total of 370 times and the follow-up periods range from 2 to 25 years. RESULTS: 25% of the patients had chronic bilateral keratitis with symptoms of intense photophobia, blepharospasm and lacrimation. On 13 patients the first symptoms appeared before the age of 4 years. Keratitis was the first presenting sign before any evidence of systemic disease in three patients, and in all patients keratitis was among the first three manifestations of the syndrome. The clinical picture from the acute to the chronic cicatricial stage is described. The best corrected visual acuity at the end of the follow-up was 0.6 or better in six patients only. Of the total material 12 patients had lenticular opacities as the manifestation of hypoparathyroidism. CONCLUSIONS: Chronic bilateral keratitis is an ocular manifestation of APECED and in its etiology both hypoparathyroidism and candidiasis may be ruled out as single causes. When an ophthalmologist is confronted with a young child with bilateral chronic keratitis with symptoms of intense photophobia, blepharospasm, lacrimation and either with mucocutaneous candidiasis or hypoparathyroidism, the patient should be referred to a pediatric endocrinological consultation for the possibility of underlying APECED.

Confocal microscopy of a patient with irregular astigmatism after LASIK reoperations and relaxation incisions.

PURPOSE: Laser-assisted in situ keratomileusis (LASIK) is widely used for correcting refractive errors. If the predicted refractive result is not achieved after the first operation, a re-operation can be performed by ablating more stromal tissue after reopening the flap. The goal of this study was to analyze, by using in vivo confocal microscopy, the morphologic changes associated with repeated LASIKs. METHODS: Clinical examination, computed corneal topography, and real-time in vivo confocal microscopy were performed on both eyes of a 50-year-old patient with induced irregular astigmatism leading to decreased best-corrected vision in the left eye after LASIK. The left cornea had been operated on 5 times (LASIK with two reoperations followed by two relaxing incisions), and the right cornea twice (LASIK with one reoperation). RESULTS: Microfolds at the level of the Bowman's layer and highly reflective particles at the flap interface were observed in both corneas. The subbasal nerve plexus was severed in the left eye. In addition, we identified epithelial material in the flap margin and inside one of the two relaxing incisions placed inferotemporally. CONCLUSION: Repeated LASIKs may stretch the flap and result in microfolding at the Bowman's layer. This and deposition of particles in the flap interface may increase with the number of reoperations, challenging the healing response. Microfolding and occurrence of foreign material in the interface may add to the irregular astigmatism and poor visual outcome after LASIK. Clinical in vivo confocal microscopy offers new possibilities for the assessment of ultrastructural changes after corneal refractive surgery.

Image analysis to improve diagnosis of exfoliation.

PURPOSE: To improve visualization of exfoliation material in standard colour photographs by image analysis. METHODS: Standard anterior segment colour photographs taken from 17 patients with known exfoliation were subjected to film scanning with a maximum accuracy of 3175 dpi. RESULTS: Before image scanning, visualization of exfoliation was classified as barely visible in 10 (59%) patients and clearly visible in 7 (41%) patients. After the image scanning, exfoliation material became clearly visible in 13 (76%) patients and could easily be demonstrated. CONCLUSION: Diagnosis of exfoliation material can be improved by standard film scanning.

Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma.

PURPOSE: Although malignant uveal melanoma disseminates predominantly hematogenously because of the absence of intraocular lymphatics, consensus about prognostic impact of microvascular density (MVD) has not been reached. This study was undertaken to investigate whether MVD, microvascular patterns, or both determine prognosis of uveal melanoma. METHODS: A population-based retrospective cohort study of melanoma-specific and all-cause mortality of 167 consecutive patients who had an eye enucleated because of choroidal or ciliary body melanoma from 1972 through 1981 was conducted. MVD was determined by counting tumor vessels in a masked fashion from areas of highest vessel density after immunostaining for CD34 epitope, factor VIII-related antigen (FVIII-RAg), and alpha-smooth muscle actin (SMA). Kaplan-Meier and Cox regression analyses of survival were performed. The association between MVD and tumor size and location, cell type, and microvascular patterns was assessed. RESULTS: MVD could be determined from 134 of 167 melanomas (80%). Based on globally highest count obtained with antibodies to CD34, MVD ranged from 5 to 121 vessels/0.313 mm2 (median, 40) and its association with presence of microvascular loops and networks (P = 0.0006), epithelioid cells (P = 0.028), and largest basal tumor diameter (P = 0.0029) was statistically significant. The 10-year melanoma-specific mortality increased with MVD (0.09, 0.29, 0.59, and 0.64, according to quartiles; P < 0.0001), as did all-cause mortality (P = 0.0022). Equivalent results were obtained with immunostaining for FVIII-RAg, whereas MVD obtained with antibodies to SMA was not associated with prognosis. Cox regression showed a hazard ratio of 2.45 (95% CI, 1.43-4.18) for presence of epithelioid cells, 1.11 (95% CI, 1.03-1.20) for largest basal diameter, 1.23 (95% CI, 1.06-1.43) for square root-transformed MVD, and 1.51 (95% CI, 1.09-2.10) for presence of loops and networks, all of which independently contributed to prognosis. CONCLUSIONS: The findings support the theory that both MVD and microvascular patterns contribute independently to prognosis in uveal melanoma in addition to cell type and size of the tumor.

Unilateral capsular glaucoma after long-standing bilateral pigmentary glaucoma.

In 1964 we treated a 42-year-old woman diagnosed to have classical bilateral pigment dispersion syndrome combined with an intraocular pressure (IOP) of up to 28 mmHg in both eyes. The patient now has a daughter, also with pigment dispersion syndrome. Miotic treatment brought the IOPs to normal, and 8 years later when the disease was in the inactive phase all treatment could be discontinued. At the age of 67 years, exfoliation deposits became visible in the right eye only, but the IOPs were still below 21 mmHg. Four years later, the pressure of the right eye rose to 31 mmHg. During the next few years all available IOP-lowering medications and laser trabeculoplasty failed, and finally trabeculectomy had to be performed to keep the pressure of the right eye under control and to halt visual field changes, which had already appeared. This case illustrates that development of exfoliation syndrome may take place irrespective of pigment dispersion, and that their simultaneous occurrence may lead to an IOP rise that is resistant to medical therapy and laser trabeculoplasty. It additionally provides further clues to the pathogenesis of capsular glaucoma.

Evaluating cataract surgery gains by assessing patients' quality of life using the VF-7.

PURPOSE: To describe the development and performance of a questionnaire designed to measure functional impairment caused by cataract. SETTING: Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS: The results of a visual-functioning index (VF-14) of 168 patients with first-eye cataract surgery were analyzed. Patients with significant comorbidity were excluded, leaving 142 patients for the final analysis. Snellen visual acuity measurements and complete preoperative and 4 month postoperative clinical status were performed by ophthalmologists. Outcome measures, including the VF-14, patient perception of trouble with vision, patient satisfaction with vision, and the cataract symptom score, were taken by nurses at the preoperative clinical examinations and at the 4 month postoperative visit. The Spearman rank correlation was used to determine which items of the VF-14 best correlated with a change in patient satisfaction. RESULTS: Seven items of the VF-14 that best correlated with patient satisfaction were selected for inclusion in a new 7-item index (the VF-7). Based on the Spearman rank correlation, the items from best to worst were nighttime driving; reading small print; watching television; seeing steps, stairs, or curbs; reading traffic, street, or store signs; cooking; and doing fine handwork. The correlation among changes in the VF-7 score and visual acuity in the operated eye was 0.17, while the correlation among changes in the VF-7 and patient satisfaction caused by cataract surgery was high (r = .56). CONCLUSION: The VF-7 was a strong predictor of change in patient satisfaction caused by cataract surgery.

Visual function after strontium-90 plaque irradiation in patients with age-related subfoveal choroidal neovascularization.

PURPOSE: To report 2-year visual and angiographic results in eyes treated with strontium plaque irradiation for subfoveal choroidal neovascular membranes (CNVM) in age-related macular degeneration. METHODS: Twenty eyes with recent subfoveal CNVM were treated with local irradiation. The impact of the treatment on visual function was evaluated by visual acuity, contrast sensitivity and reading speed testing. RESULTS: At 12 months visual acuity had improved or remained the same in 9/ 20 eyes (45%). At 24 months visual acuity was stable in 5/18 eyes (28%). Eyes with signs of CNVM regression (13/18, 72%) lost a mean of 3.3 lines, but eyes with recurrent CNVM lost a mean of 5.1 lines of vision. The mean contrast sensitivity was better in the irradiated eyes than in the fellow eyes with late age-related macular degeneration at 24 months. Six of 17 irradiated eyes (35%) could read at least some words at 24 months. CONCLUSIONS: Visual function decreases in patients treated with strontium irradiation, but less in eyes showing regression of the CNVM than in eyes with further growth of the CNVM.

Microvascular loops and networks as prognostic indicators in choroidal and ciliary body melanomas.

BACKGROUND: Malignant melanoma of the ciliary body and choroid of the eye is a tumor that disseminates frequently, and 50% of the diagnosed patients die within 10 years. We investigated the hypothesis that, by histopathologic analysis of the arrangement of microvessels (i.e., small blood vessels) in loops and networks, we might be able to differentiate better those patients with a favorable prognosis from those with a poor prognosis. METHODS: We conducted a population-based, retrospective cohort study of melanoma-specific and all-cause mortality for 167 consecutive patients who had an eye surgically removed because of malignant choroidal or ciliary body melanoma during the period from 1972 through 1981. Microvascular loops and networks were evaluated independently by two pathologists who were unaware of patient outcome. RESULTS: Microvascular patterns could be assessed in 134 (80%) of 167 melanoma specimens. The 10-year probability of melanoma-specific survival was worse if microvascular loops (0.45 versus 0.83; two-sided P<.0001) and networks (0.41 versus 0.72, two-sided P<.0001) were present. In multivariate Cox regression analysis of melanoma-specific survival, the hazard ratios were 1.66 (95% confidence interval [CI] = 1.19-2.30) for the presence of loops and networks as a combined three-category variable, 2.36 (95% CI = 1.37-4.05) for the presence of epithelioid cells, 1.11 (95% CI = 1.03-1.19) for the largest basal tumor diameter (evaluated as a continuous variable), and 2.14 (95% CI = 1.25-3.67) for ciliary body involvement. CONCLUSIONS: Patients with malignant uveal melanoma who have a favorable prognosis can be distinguished from those with a poor prognosis by histopathologic analysis of microvascular patterns in uveal melanoma tumor specimens.

Prospective evaluation of external ocular microbial growth and aqueous humor contamination during cataract surgery.

PURPOSE: To analyze the route of aqueous humor contamination leading to the development of postoperative endophthalmitis. SETTING: Department of Ophthalmology, University of Helsinki, Finland. METHODS: Forty-nine eyes of 49 patients (31 having phacoemulsification and 18 extracapsular cataract extraction [ECCE]) participated in the study. Four bacterial cultures were taken: preoperative conjunctival swab, lid margin culture, intraoperative lacrimal lake sample, and immediate postoperative anterior chamber fluid sample. RESULTS: Preoperative lid margin cultures were positive in 59.2% of eyes, conjunctival cultures in 69.4%, and lacrimal lake cultures in 24.9%. Four aqueous humor samples (8.2%) showed bacterial growth in the anterior chamber aspirate: 3 in the phacoemulsification and 1 in the ECCE group. The bacteria isolated in this study, Staphylococcus epidermidis and Propionibacterium acnes (2 positive isolates each) were sensitive to the preoperative topical antibiotics used. No aqueous humor sample or any from other locations showed gram-negative microbe growth. The most frequently recovered microbes in all samples collected from the 3 other sources were S epidermidis and other coagulase-negative staphylococcus species, followed by P acnes and other propionibacterium species. Staphylococcus aureus, and diptheroids. CONCLUSION: The ocular surface significantly contributed to the transmission of microbes into the eye during cataract surgery. These microbes could not be eradicated by topical preoperative antibiotics. However, no patient developed postoperative endophthalmitis. Natural defense mechanisms appear to fend off a minor inoculum with these microbes of relatively low pathogenicity.

Comparative immunohistochemical oestrogen receptor analysis in primary and metastatic uveal melanoma.

BACKGROUND: The investigation reported here was carried out to determine the oestrogen receptor status of metastatic and primary uveal melanomas. METHODS: A series of 23 primary and 24 metastatic formalin-fixed paraffin-embedded choroidal melanomas were analysed immunohistochemically with the monoclonal antibody (MAb) 1D5 using the avidin-biotinylated peroxidase method and antigen retrieval with microwaves. Melanophages were identified with MAb PG-M1 to macrophages. RESULTS: None of the primary or metastatic melanomas contained tumour cells that would have shown a nuclear immunoreaction for oestrogen receptors with MAb 1D5. However, in 20 of the 23 primary tumours and in 14 of the 24 metastases a variable number of infiltrating cells showed a strong positive cytoplasmic immunoreaction with MAb 1D5. The cells contained pigmented cytoplasmic granules that resisted bleaching of melanin and their cytoplasm was strongly labelled with MAb PG-M1, identifying them as cross-reacting macrophages. CONCLUSION: Oestrogen receptors can not be used as a prognostic indicator if anti-oestrogen therapy is considered for treatment of metastatic uveal melanoma. However, because anti-oestrogens also act by other mechanisms on both tumour and host tissues, the lack of oestrogen receptors does not automatically negate their therapeutic effect in disseminated melanoma.

Immunohistological localization of the MrkD adhesin in the type 3 fimbriae of Klebsiella pneumoniae.

The adhesive minor protein MrkD of the type 3 fimbria of Klebsiella pneumoniae was expressed and purified from Escherichia coli as a fusion protein with an N-terminal polyhistidine tail. Polyclonal antibodies raised against MrkD specifically recognized the MrkD peptide in Western blots of fimbrial preparations. Immunoelectron microscopic analyses showed that the anti-MrkD immunoglobulins bound to the tip of the plasmid-encoded variant of the type 3 fimbria of K. pneumoniae, whereas no binding to the chromosomally encoded MrkD-deficient type 3 fimbrial variant of K. pneumoniae was detected. Immunoglobulins from an antiserum raised against purified type 3 fimbrial filaments bound laterally to both type 3 fimbrial variants. The anti-MrkD antibodies also bound to the tip of a papG deletion derivative of the E. coli P fimbria complemented with mrkD, indicating that MrkD structurally complements a PapG mutation in the P fimbria of E. coli.

Outcomes of small incision cataract surgery.

PURPOSE: To compare cataract surgery outcome measures 4 months postoperatively and determine their association with changes in the eye's functional state. SETTING: Department of Ophthalmology, Helsinki University Central Hospital, Finland. METHODS: This longitudinal study comprised 219 consecutive patients having first-eye or second-eye cataract surgery by one surgeon. In most patients, the technique consisted of small-incision cataract surgery with in-the-bag intraocular lens implantation. Patients were interviewed and clinical data obtained preoperatively and 4 months postoperatively. Adverse events occurring within 24 hours and 4 months postoperatively were compared with changes in global measures of vision. Surgical success in terms of surgically induced astigmatism (SIA) was measured at 4 months using vector analysis of the changes in astigmatism and defining the extent to which the surgical goal was achieved. The association between the surgical astigmatism goals and global measures of vision was analyzed. RESULTS: The percentage of patients showing improvement 4 months after first-eye cataract surgery varied by outcome measure: Snellen visual acuity (95.0%), VF-14 score (89.4%), satisfaction with vision (80.1%), self-reported trouble with vision (75.8%), and cataract symptoms (75.1%). Changes in Snellen acuity after second-eye cataract surgery were similar but VF-14 changes were significantly less than after first-eye surgery. Changes in global measures of vision were also better after first-eye surgery. The correlation between the change in VF-14 score and global measures of vision was stronger than between the change in Snellen acuity and the same general outcome measures. A good correlation was also seen between the changes in VF-14 scores and cataract symptoms. Mean SIA in all eyes was 0.2 diopter (D) +/- 0.7 (SD); 91.2% were within +/- 1.0 D of preoperative values. Failure to achieve surgical astigmatism goals was not associated with patients in whom global measures of vision did not improve, nor was there a correlation between adverse events occurring within 24 hours or 4 months postoperatively and global measures of vision. The only association was between ocular comorbidity or potential risk factors of phacoemulsification and adverse events seen within 24 hours and at 4 months. CONCLUSION: Estimates of the proportion of patients benefiting from cataract surgery varied with the outcome measure used to determine benefit. The change in the VF-14 score was a better measure than Snellen acuity of the benefit of cataract surgery.