Diagnosis of a neonatal ophthalmic discharge, Ophthalmia neonatorum, in the molecular age: investigation for a correct therapy.

An early double case of acute Ophthalmia neonatorum in 3-day-old twins is reported. Culture of eye swabs showed a wide bacterial polymorphism, in which common bacteria, such as Klebsiella pneumoniae, Streptococcus pneumoniae, Corynebacterium ulcerans and other Enterobacteriaceae, coexisted with atypical Mycoplasmataceae and Chlamydiaceae from resident cervical-vaginal maternal microbiota. The neonates were in an apparently healthy state, but showed red eyes with abundant greenish-yellow secretion, mild chemosis and lid edema. The maternal cervical-vaginal ecosystem resulted differently positive to the same common cultivable, atypical bacteria culturally and molecularly determined. This suggested a direct maternal-foetal transmission or a further foetal contamination before birth. An extended culture analysis for common bacteria to atypical ones was decisive to describe the involvement of Mycoplasmas (M. hominis and U. urealyticum) within the scenario of the Ophthalmia neonatorum in a Caucasian couple. The introduction of a routine PCR molecular analysis for Chlamydiaceae and N. gonorrhoeae allowed to establish which of these were present at birth, and contributed to determine the correct laboratory diagnosis and to define an adequate therapeutic protocol obtaining a complete resolution after one year for culture and atypical bacteria controls. This study suggests to improve the quality of laboratory diagnosis as unavoidable support to a correct clinical diagnosis and therapy, in a standardized modality both for swabbing and scraping, to check the new-born microbial programming starting in uterus, overtaking the cultural age to the molecular age, and to revise the WHO guidelines of SAFE Strategy for trachoma eye disease, transforming it into SAFES Strategy where the S letter is the acronym of Sexual ecosystem and behavioural valuation/education.

Enigmatic question of early reactive arthritis disclosed after researches of mycoplasmas, Chlamydia trachomatis and enteropathogens following the holistic vision of human being.

An HLA-B27 genetic profile patient is fully investigated by molecular analyses after an anamnestic assessment of multi-site ecosystems, following the holistic vision of human being.VDRL and Widal-Wright (WWR) resulted positive, showing at Wright’s reaction a title of 1:40. Of all the enzymatic activities measured, only the ALP enzymatic pool activities showed a low increasing value of 297 U/L. Of all later acute phase proteins, Only C3 c protein value (127 mg/dL) and fibrinogen (376 mg/dL) were altered. Cultural and molecular oropharyngeal ecosystem investigation resulted significantly positive to Mycoplasmas(Mhand Uu) and Chlamydia trachomatis(Ct) together with a spread of saprophytic flora. From an accurate anamnesis, several and severe uro-genital clinical symptomatology emerged from birth until the beginning of rheumatologic symptomatologies that were confirmed by oldest Mh, Uu and Ctsilent chronic infections between these ecosystems. The molecular HPV research was negative, while the Thin prep pap-test was indicative of vaginosis and cellular reactive changes associated with inflammation. Parasitological research resulted positive for presence of 5-7 newly-formed G. lambliacysts for microscopic field, while digestibility test was positive for presence of several free fatty acid crystals. The remarkable presence of indigested meat fibre and several mucous dense filaments were observed. The pH value was 6.5, while blood faecal test was positive. The values observed were: ferritin 12 microg/L (10-120), total iron-binding capacity (TIBC) 310 &mgr;g/dL (300+-20), unsaturated iron-binding capacity (UIBC) 286 microg/dL (200-220) and iron seric level 24 microg/dL (60-130). Faecal research highlighted a very scarce presence of E. coli, resulting in 102 UFC/g of stool. Of all enteroinvasive pathogens, researched by molecular analyses, only Yersinia spp. was positive. After several specific cycles of antibiotic and antinflammatory therapies, the patient improved its general health condition considerably and showed almost complete regression of aching inguinal lymph node inflammation. In a picture of a worsening inflammatory process, produced by pathogens like Mycoplasmas, chronic silent or low grade inflammation atypical agents, in young HLA-B27 positive patient, VDRL test resulted positive. This value represents the first non-specific unique spy to reveal the precocious immunological signal in order to register the beginning of early innate immune system decay, keeping in mind that mycoplasmal and chlamydial infections are the triggering of cancer in patients genetically susceptible.

Can latent synergism of intestinal pathogens be responsible for inflammaging process causing Reiter's syndrome in a young patient HLA-B27 infected by atypical pathogens? A holistic view and clinical biochemical reinterpretation.

A case of a genetically HLA-B27 patient fully investigated by molecular analyses, following a holistic vision and an anamnestic assessment of multi-site ecosystems is repeated. VDRL, Lupus anti-coagulant (LAC) and Widal-Wright (WWR), resulted positive. The antibodies (IgG/IgA anti-Ct) against chronic Chlamydia trachomatis inflammation were positive. In the context of all the enzymatic activities in reference range, the AMS and the ALP enzymatic activities showed an increasing trend and a time course augment depending respectively. Cultures, parasitological, digestibility tests and molecular analyses were then performed to investigate the different human ecosystems. Parasitological research and digestibility test were performed, resulting a latent chronic bowel inflammation, including certain enteroinvasive pathogens, such as, Salmonella, Shigella, Yersinia and Campylobacter (Enteric Pathogens Group, EPG) and Escherichia Coli pathogens (Escherichia Coli Pathogens Group, ECPG). The Salmonella typhi-DNA resulted positive, while 90% of the total microbic charge (TMC) was represented by C. freundi in culture analyses. Interpreting the VDRL positive test as early triggering of autoimmune disease, a few acute phase proteins as a pauci-symptomatic chronic phlogistic process, the amylase and alkaline phosphatase alterations as tissue markers of early intestinal inflammation, the Widal's reaction positivity together with the precocious clinical and faecal manifestations, this study suggests the prime triggering role of these atypical pathogens to cause a chronic low grade autoimmune response against the tissue/organ susceptible target, causing inflammaging phenomenon in young patient with chronic latent infection by Salmonella typhi, leading to Reiter's syndrome, in HLA-B27 positive patient.

Michelangelo's eye disease.

Charged by the Pope Julius II for painting the Cappella Sistina in Rome (between 1508 and 1512), Michelangelo worked in an elevated scaffolding, in an anomalous position with dyes (including poisoning lead salts) and solvents (such as toxic turpentine) dripping on his face and continuously inhaling, in a dim environment illuminated only with oil lamps and candles, as he described himself and sketched in a sonet addressed to Giovanni da Pistoia. In 1510 he began suffering from eye disease: the main symptom was the necessity to elevate the document he was reading up to the level of his eyes. This defect disappeared few months after he finished painting his masterpiece. We hypothesize that the Michelangelo's eyes disease was a form of acquired and transitory nystagmus induced by the many hours he spent in up gaze, with a skew deviation, a form of ocular tilt reaction resulting from the impairment of spatial sensitivity (inversion illusion) due to the persistence of the artist's head in a horizontal position, looking upward.

Jugulodigastric lymph node inflammation derived from chronic atypical oropharyngeal phlogosis recurring annually after flu virus vaccination: a holistic vision of a clinical case solved after chlamydicidal antibiotic therapy.

In this report, we evaluated the case history of a patient with longstanding chronic pharyngitis who had periodic clinical manifestation for three years after a flu vaccine administration, and after various treatments tried to resolve the chronic pharyngitis with unsuccessful antibiotic and anti-inflammatory therapies. The patient occasionally presented a slight ocular inflammation, while dysuria occurred after sexual activity. The search for common pathogens by use of pharyngeal swabs resulted only in Corynebacterium ulcerans growth. After this first result, we focused our investigations on ocular and uro-genital infections of Chlamydiaceae (Ct and Cp) and Mycoplasmataceae (Mh and Uu) families. We examined the patient?s pharynx using molecular and culture techniques from three different sites. Although several infectious agents, including viruses and bacteria, causing chronic pharyngitis are reported in the literature, these ocular and uro-genital pathogens are seldomly routinely investigated in the same patient in ORL. Furthermore, while episodes of chronic pharyngitis is one of the most common clinical manifestation in ENT patients, these atypical pharyngitis represent ever-increasing infections which must always be considered and researched by suitable instruments such as PCR. Only from the collection of detailed medical history and careful observations of clinical manifestation, indicative of an oral chronic pathologic phenomenon of low intensity initiated several years previously, starting with sudden outbreak and relapse like a bout of flu, we suggest to study these atypical infecting agents frequently localized in the urogenital human area, awhich would allow to highlight and to recognize these clinical cases that manifest themselves as chronic inflammation of jugulodigastric lymph nodes, remaining still unrecognized and rarely associated to chlamydial infection, confused with the response to flu vaccination. After several specific cycles of antibiotic therapy, the patient's health improved considerably and showed almost complete regression of jugulodigastric lymph node inflammation.

Ocular clinical pictures disclosed by PCR molecular diagnosis of Chlamydia trachomatis infection performed following the appropriate sampling modality in ocular ecosystem.

Four clinical cases regarding the correct diagnosis of early ocular Chlamydia trachomatis (Ct) inflammation, performed by two different modalities on the ocular ecosystem, are discussed. The present study was carried out in parallel using a cotton flock ocular swab and the scraping of upper lid conjunctiva. The ocular samplings were carried out by a first ocular swab from inner canthus and fornix, while the second by a conjunctival scraping from upper the conjunctiva of four patients. In the first case, by ocular swab, all samples resulted negative to Ct-DNA research by PCR, while the cultural analyses showed a growth of saprophytic and opportunist germs in all patients. No growth micetes resulted. On the contrary, in the second case, by conjunctival scraping, three of four samples were positive to Ct-DNA research. No fungal growth was observed, while only the 3rd patient, negative to Ct-DNA research, showed microbial growth. Our study, carried out with two different modalities of sampling on different areas of the same ecosystem, showed different results, demonstrating the importance of sampling accuracy for chlamydial research by molecular analysis in PCR, during the slight phase of inflammation. These initial data indicate that laboratory diagnosis by PCR for precocious Ct infection, not revealed clinically, could represent the first step for a correct diagnostic procedure, eliminating one of the critical points, allowing an accurate, effective and precocious antibiotic therapy. We hypothesize that only by following these correct procedures of sampling during the early phase of chlamydial inflammation, in the future, will it be possible to reduce a pejorative evolution of this worsening disease in people genetically susceptible, building a more efficacious Public Health program of prevention against chronic conjunctivitis and to favour a major prevention of trachoma in endemic areas.

Molecular approach by PCR is the best method to detect the presence of Chlamydia trachomatis and to define the true agent of ocular bacterial inflammation.

Chlamydia trachomatis (Ct) is an atypical agent for acute, subclinical and chronic conjunctivitis in developed countries, as stated by the International League against Trachoma. In order to evaluate the presence of Ct, from a total of 3,520 patients visiting the consulting room of the Eye Clinic of the University of Chieti, Italy from 2006-2008, we enrolled 171 patients affected by occasional mild, moderate or severe conjunctivitis in a three-arm prospective open study, using traditional analysis such as Immune Fluorescent Assay and Enzyme–Linked Fluorescent Assay (IFA and ELFA) and molecular analysis with Polymerase Chain Reaction (PCR) procedure for Ct DNA research (Ct DNA). At the same time, microbiological culture was carried out for common germs and mycetes. These patients were analyzed at different subsequent times. In the first arm (Group A) of 82 patients with IFA and ELFA only 10 people (12.2%) resulted positive to Ct infection with both methods. The presence of Ct was never alone, but always overlapped with contaminants, like corynebacteria, staphylococci, streptococci and colonbacteria, randomly distributed, while no growth of mycetes was observed. Of these positive patients, only one 47-year-old female, suffering from a moderate form of ocular chlamydial infection, showed serological conversion against this infection; furthermore, this female had also been suffering from reactive arthritis for sometime. In the second arm (Group B) of 89 patients, we carried out PCR for Ct detection: 82 (94.25%) were found positive to Ct – DNA research, with common germ growth randomly associated, without sex or age prevalence, as in group A; no mycetes were found. The third arm (Group C) included 37 negative patients from Group A with severe or moderate chronic conjunctivitis, randomly recruited between relapsing cases, with the addition of the single previously positive seroconversion case, for a total of 38 patients, who were re-evaluated by PCR Ct-DNA analysis. All these patients, negative to IFA and ELFA, were positive to Ct-DNA analysis. These data indicate a higher rate of Ct infection in patients with severe or moderate chronic conjunctivitis, resistant to usual therapies even after eradication of common germs, thus showing the advantage of introducing this molecular technique of analysis in mild to severe chronic or recurrent conjunctivitis.

Color vision and macular recovery time in epileptic adolescents treated with valproate and carbamazepine.

Visual dysfunction has been reported in patients diagnosed with epilepsy. Some of these visual disturbances may be attributable to either the disease process, or the anticonvulsant therapy prescribed to control the seizures. The aims of our study were to evaluate whether color vision and macular function are impaired in epileptic adolescents, to study if the monotherapy with valproic acid (VPA) and carbamazepine (CBZ) can affect color vision and macular function and to determine the possible relationship between color vision, retinal function and antiepileptic drugs (AEDs) dosage and their serum concentrations. We examined 45 (16 male and 29 female, mean age +/- SD, 15.71 +/- 2.01 years) Caucasian epileptic patients suffering from various types of cryptogenic epilepsy before the beginning of therapy and after 1 year of VPA or CBZ monotherapy and 40 sex- and age-matched healthy controls. Color vision was assessed by Farnsworth Munsell (FM) 100-hue test and total error score (TES) was evaluated. This test consists of colored caps: the testee has to arrange the caps according to their colors macular function was assessed by nyctometry evaluating initial recovery time (IRT) and summation method (SM). This test evaluates visual acuity after a period of intense illumination of macula. Analysis of variance was used to evaluate the difference between controls and patients; moreover, Pearson's correlation test have been performed. Before the beginning of therapy, there were no differences in color vision and macular function between controls and epileptic patients. After 1 year, the patients, treated with VPA or CBZ, showed a deficit in FM 100-hue test. At nyctometry, all patients showed no significant variation of macular function between baseline evaluation and second evaluation at end of the follow-up. Our study demonstrates that, in our group of epileptic patients, epilepsy per se does not affect color vision and retinal function. In contrast, after 1 years of therapy with VPA and CBZ these patients showed a deficit in FM 100-hue test although nyctometry evaluation continued to be normal allowing to exclude an impairment in macular function. Further investigations are required to determine the pathophysiological alteration(s) that are at the basis of color perception defects.

Color vision in epileptic adolescents treated with valproate and carbamazepine.

OBJECTIVE: The aims of our study were to evaluate whether deficits in color vision exist in epileptic adolescents, to study if monotherapy with valproic acid (VPA) and carbamazepine (CBZ) can affect color vision, and to determine the possible relationship between abnormal color vision tests and AEDs dosage and their serum concentrations. PATIENTS: We examined 45 epileptic patients before the beginning of therapy and after 1 year of VPA or CBZ monotherapy and 40 sex- and age-matched healthy controls. METHODS: Color vision was evaluated with Farnsworth Munsell 100 (FM100) hue test and achromatic and short-wavelength automated perimetry (SWAP). STATISTICAL ANALYSIS: To evaluate intergroup differences we used ANOVA with Scheffe's post hoc test, when appropriate. Repeated measures ANOVA was used to evaluate the intragroup modifications of total error score (TES) and perimetric threshold during the follow-up. Pearson's correlation test was performed to correlate chromatic sense and perimetric data and AEDs dosage and serum concentrations. RESULTS: Before the beginning of therapy, there were no differences in central color vision and SWAP between controls and epileptic patients. After 1 year, patients treated with VPA or CBZ showed a deficit in FM100 hue test and SWAP parameters while no significant deficit was found in achromatic perimetry. In particular, with the FM100 hue test a higher number of errors was found in both groups of patients (CBZ patients: 166.00 +/- 27.72 TES; VPA patients: 151.19 +/- 44.09, P < 0.001) in comparison with controls (controls: 109.29 +/- 24.73) and baseline values (CBZ patients: 110.65 +/- 22.9; VPA patients 107.43 +/- 21.70). With SWAP patients of both groups showed significant variation of foveal threshold (controls: 21.07 +/- 2.01 dB; CBZ patients: 19.35 +/- 1.32, P < 0.001; VPA patients: 18.88 +/- 1.89, P < 0.001), full-field mean threshold perimetric sensitivity (controls: 18.50 +/- 1.24 dB; CBZ patients: 16.60 +/- 1.47, P < 0.001; VPA patients: 16.23 +/- 1.55, P < 0.001) and mean threshold perimetric sensitivity of the three evaluated subareas of the visual field (area 1 controls: 21.01 +/- 1.15; CBZ patients: 19.45 +/- 1.74, P = 0.001; VPA patients: 18.25 +/- 1.61, P < 0.001; area 2 controls: 18.40 +/- 1.43; CBZ patients: 16.07 +/- 1.58, P +/- 0.001; VPA patients: 16.13 +/- 1.46, P = 0.001; area 3 controls: 17.20 +/- 1.49; CBZ patients: 14.28 +/- 1.51, P < 0.001; VPA patients: 14.31 +/- 2.90, P = 0.001). CONCLUSIONS: Our study demonstrates that treatment with VPA or CBZ can affect significantly both central and paracentral color vision after a short treatment period.

Static perimetry and diabetic retinopathy: a long-term follow-up.

In order to evaluate if central static perimetry is useful to identify patients at risk of developing diabetic retinopathy, 60 (27 male, 33 female) adolescents and young adults (mean age, 15.9 years) with insulin-dependent diabetes mellitus were studied prospectively. No patient showed fluorescein angiographic signs of retinopathy initially. The patients were evaluated at the beginning of the study and after 8 years. At the beginning of the study, mean defect in the population was -2.34 dB as determined by perimetry; no patient showed significant impairment of foveal threshold (mean, 33.17 dB). After 8 years of follow-up, 7 patients had developed fluorangiographic signs of retinopathy. Life-table analysis showed that the overall probability of retinopathy development was significantly higher in subgroups of patients with mean sensitivity in areas 2 and 3 below the cutoff. These results suggest that central static perimetry is a useful tool in predicting the development of retinopathy in children with insulin-dependent diabetes mellitus who do not have fluorescein angiographic signs of retinopathy. This tool can help the physician to identify those patients at risk of developing fluorangiographic signs of retinopathy.

Treatment of retinal tears and lattice degenerations in fellow eyes in high risk patients suffering retinal detachment: a prospective study.

BACKGROUND/AIMS: Fellow eye prophylaxis for retinal detachment (RD) is still a controversial issue since opinions are not unanimous regarding the kind of lesions to be treated or the method of treatment. This prospective clinical study aimed to follow the course of vitreoretinal conditions in 150 high risk fellow eyes. METHODS: 150 consecutive patients with unilateral rhegmatogenous RD were included in this study. Inclusion criteria were good explorability of fellow eye retinal periphery and one of the following conditions in the fellow eye-aphakia, pseudophakia with capsulotomy, high myopia (>-6D), contralateral eye to a giant retinal tear. Prophylactic treatment (photocoagulation or scleral buckling) was performed in the presence of retinal tears and lattice degenerations. The state of the vitreous body was determined at the beginning of the study and at the end, when RD occurred. RESULTS: Follow up ranged from 36 to 132 months. 95 fellow eyes were subjected to laser treatment; five eyes underwent prophylactic surgical treatment. Initially, in the treated group posterior vitreous detachment (PVD) was present in 100 eyes (100% of cases), but as a complete PVD only in 42 of them (42%). 10 eyes in the treated group developed RD during the follow up period. In five of these cases the partial PVD had progressed and a retinal tear in a previously healthy area was the cause of the retinal detachment. In the other five eyes RD apparently developed from previously treated lesions. Progression of PVD was evident in four out of these five eyes. The untreated eyes had no visible degenerative lesions. During follow up eight eyes developed RD. These eyes had no PVD at the beginning of the study, but showed a partial PVD at the time of the diagnosis of RD. CONCLUSION: Fellow eyes with pre-existing retinal tears and PVDs can go on to retinal detachment in spite of laser prophylactic treatment. When PVD is not detectable or a partial PVD is present, the progression of posterior vitreous separation can account for retinal tears and RDs arising in formerly healthy areas.

Topical lomefloxacin 0.3% twice daily versus tobramycin 0.3% in acute bacterial conjunctivitis: A multicenter double-blind phase III study.

AIMS/BACKGROUND: To evaluate in a double-masked comparative, prospective, randomized multicenter trial the efficacy of lomefloxacin 0.3% eye drops twice daily and of tobramycin eye drops 4 times daily in patients with acute bacterial conjunctivitis. METHODS: Ninety-nine subjects were enrolled: 50 were treated with lomefloxacin 0.3% eye drops twice daily and 49 with tobramycin 0.3% eye drops 4 times daily. In all patients, conjunctival swabbing and assessment of objective signs and of subjective symptoms were performed. RESULTS: There was no statistical difference for any individual sign or symptom or for the sum score of either key or other signs and symptoms at any of the examination days. The sum score of both key and other signs and symptoms decreased in both groups at day 3-4 as compared to baseline values (p < 0.0001). The decrease in both these scores continued significantly from day 3-4 to day 7-8 (p < 0.05) and was similar in the two treatment groups (p > 0.4). The lowest resistance rate was seen in lomefloxacin (3.5%) and in neomycin (7.0%), while tobramycin showed resistance in 10 out of 88 resistance strains (11.4%). CONCLUSION: Both lomefloxacin 0.3% twice daily and tobramycin 0.3% administered 4 times daily were well tolerated and showed a high degree of clinical and microbiological efficacy in the treatment of acute bacterial conjunctivitis. Lomefloxacin caused less resistance than other antibiotics evaluated.

In vitro viability of external eye microbial flora in hydroxy-propyl-methylcellulose.

The aim of this study was to verify the in vitro influence of various dilutions of a viscoelastic substance containing 2% hydroxy-propyl-methylcellulose (HPMC) on the viability of some microbial strains representative of the normal flora of the external eye. Pure reference strain cultures of Candida albicans, Pseudomonas aeruginosa, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis and a fresh clinical isolate of Proteus mirabilis were selected for this study. Serial twofold dilutions of 2% HPMC, prepared so as to obtain a final concentration ranging from 50 to 0.78% of the product in sterile saline solution (0.85% NaCl), were taken out with a pipette that delivered 1.0 ml per tube. One hundred microliters of the abovementioned microbial inocula, used for the evaluation of the positive control of the test organism, were dispensed into each tube. After 24 h of incubation, 100 microl of samples were taken from each tube and plated into the specific medium for the growth of the test organism. After 24-48 h of incubation, these agar plates were examined and the colony-forming-unit count of each test organism was compared to the corresponding total colony count, acting as a positive control, in order to determine the quantitative variation of the test organism grown in the presence of the viscoelastic compounds. C. albicans and P. aeruginosa showed a statistically significant increase in growth with HPMC dilutions varying from 1:2 to 1:16. P. acnes and P. mirabilis growth was significantly reduced by all dilutions except for the 1:128 one. S. epidermidis growth was also significantly reduced in the presence of HPMC dilutions varying from 1:2 to 1:64. S. aureus growth was not significantly influenced. The viability of P. aeruginosa in HPMC dilutions needs to be carefully considered because of the ability of this organism to induce endophthalmitis, and the possibility that during cataract surgery, a small amount of HPMC may be left in the eye, trapped behind the intraocular lens optic.

A 12-month, randomized, double-masked study comparing latanoprost with timolol in pigmentary glaucoma.

OBJECTIVE: To compare the efficacy and side effects and the effect on aqueous humor dynamics of 0.005% latanoprost applied topically once daily with 0.5% timolol given twice daily for 12 months to patients with pigmentary glaucoma. DESIGN: Prospective, randomized, double-masked, clinical study. PARTICIPANTS: Thirty-six patients affected with bilateral pigmentary glaucoma controlled with no more than a single hypotensive medication were enrolled in the study. INTERVENTION: The sample population was randomly divided into 2 age- and gender-matched groups each of 18 patients. Group 1 received 0.005% latanoprost eyedrops once daily and the vehicle (placebo) once daily; group 2 was assigned to timolol 0.5% eyedrops twice daily. MAIN OUTCOME MEASURES: Diurnal curves of intraocular pressure (IOP) were performed on the baseline day and after 0.5, 3, 6, and 12 months of treatment. The IOP measurements were performed at 8:00 AM, 12:00 noon, 4:00 PM, and 8:00 PM. Outflow facility ("C") was measured on the baseline day and on the last day of the study with a Schiotz electronic tonometer. A two-tailed Student's t test for paired or unpaired data was used for statistical evaluation of differences between treatment and baseline values or between the latanoprost and timolol group. Diurnal IOP measurements were compared hour by hour. Mean values of the two eyes IOP and "C" were used for analysis. RESULTS: Compared with baseline measurements, both latanoprost and timolol caused a significant (P < 0.001) reduction of IOP at each hour of diurnal curve throughout the duration of therapy. Reduction of IOP was 6.0 +/- 4.5 and 5.9 +/- 4.6 with latanoprost and 4.8 +/- 3.0 and 4.6 +/- 3.1 with timolol after 6 and 12 months, respectively. Comparison of mean diurnal measurements with latanoprost and timolol showed a statistical significant (P < 0.001) difference at 3, 6, and 12 months. Mean "C" was found to be significantly enhanced (+30%) only in the latanoprost-treated group compared with the baseline (P = 0.017). Mean conjunctival hyperemia was graded at 0.3 in latanoprost-treated eyes and 0.2 in timolol-treated eyes. A remarkable change in iris color was observed in both eyes of 1 of the 18 patients treated with latanoprost and none of the 18 patients who received timolol. Darkening of the peripheral iris stroma was suspected in two patients treated with latanoprost. In the timolol group, heart rate was significantly reduced from 72 +/- 9 at baseline to 67 +/- 10 beats per minute at 12 months. CONCLUSIONS: Although further studies may need to confirm these data on a larger sample and to evaluate the side effect of increased iris pigmentation on long-term follow-up, in patients with pigmentary glaucoma, 0.005% latanoprost taken once daily was well tolerated and more effective in reducing IOP than 0.5% timolol taken twice daily.

A family with autosomal dominant distal arthrogryposis multiplex congenita and brown syndrome.

Arthrogryposis multiplex congenita is a heterogeneous condition found in a number of different disorders and characterized by congenital joint contractures. We describe typical signs of congenital Brown syndrome (inability to elevate the affected eye actively or passively in full adduction) in three relatives with distal arthrogryposis multiplex congenita. We found a thickening of the superior oblique muscles in these patients with pain and increased intraocular pressure in upgaze. The pathogenesis of clinical and morphological findings is discussed. The association of Brown syndrome with distal arthrogryposis multiplex congenita has not been previously reported and provides us with an important point of reference in the understanding of both syndromes.

Dry eye in allergic conjunctivitis: role of inflammatory infiltrate.

Dry-eye associated symptoms are frequently present in patients affected with allergic conjunctivitis. We evaluated the relationship between ocular inflammation and the tear film parameters in patients affected with chronic allergic conjunctivitis. Eighty-two subjects (age 23.00 ± 7.61: range 10-40) affected with chronic allergic conjunctivitis and thirty age- and sex matched healthy controls were enrolled. In all patients tear film qualitative and quantitative tests were performed. To determine the immune activation state, conjunctival biopsies were obtained from the inferior conjunctival fornix. Immunocytochemical markers for CD45RO, CD8, CD20 and EG2 (monoclonal antibody binding eosinophil cationic protein) were evaluated semiquantitatively. All tear film tests were found altered. They were reduced in allergic patients (p<0.001). In conjunctival biopsies of allergic patients a very high number of CD45RO+ and EG2+ cells were found (p<0.001): a lower number of CD45RO+ cells and no EG2+ cells in control biopsies were found. Multivariate analysis showed a significant relationship between tear tests and conjunctival infiltrate (CD45RO+ and EG2+): The tear film alterations are strictly related to the conjunctival immune infiltration. In particular, the reduction of the mucin-related component of tear film can be related to the toxic effect of the granule cationic proteins released by the conjunctival activated eosinophils (EG2+ cells).

Delayed post-operative use of 5-fluorouracil as an adjunct in medically uncontrolled open angle glaucoma.

PURPOSE: The current study was performed to evaluate the efficacy and safety of late post-operative use of subconjunctival 5-fluorouracil (5-FU) with ocular massage (OM) after trabeculectomy with or without intraoperative mitomycin C (MMC) in patients with medically uncontrolled primary open angle glaucoma (POAG). METHODS: Initial trabeculectomy was performed in 60 eyes of 60 consecutive patients with medically uncontrolled POAG. Thirty eyes (group 1) were randomly assigned to intraoperative MMC (0.2 mg/ml for 3 min) and 30 (group 2) were randomised to standard trabeculectomy. During the first 3 months post-operatively OM and subconjunctival injections of 5-FU (5 mg in 0.5 ml of balanced salt solution) were performed in both groups every time the clinical evaluation suggested imminent bleb failure. Suture lysis was not performed in any patient. RESULTS: Follow-up ranged from 14 to 53 months (mean 30.17, SD 9.23) in trabeculectomy + MMC treated eyes and from 6 to 54 months (mean 27.37, SD 10.83) in trabeculectomy treated eyes. During the first 3 months of follow-up OM and subconjunctival injections of 5-FU were performed in 14 cases in group 1 and in 18 cases in group 2 (p = NS). A positive response to OM was obtained in 14 of 14 eyes and in 14 of 18 eyes in group 1 and in group 2, respectively (p = 0.042). The difference in post-operative mean IOP between the two groups was statistically significant at each time interval studied (p < 0.001). Success (complete or qualified) was achieved in 50 of 60 eyes (83.33%): 28 (93.3%) in the trabeculectomy + MMC treated group and 22 (73.3%) in the trabeculectomy treated group (p = 0.039). Among the complications seen, the incidence of bleb fibrosis was higher in group 2 (p = 0.0026). By means of post-operative treatment four nonrandomised subgroups were identified: intraoperative MMC + post-operative 5-FU, intraoperative MMC + no post-operative 5-FU, no intraoperative MMC + post-operative 5-FU, no intraoperative MMC + no post-operative 5-FU. The eyes treated with intraoperative MMC and post-operative 5-FU had a better long-term (48 months) cumulative probability of success (100%); treatment with intraoperative MMC or post-operative 5-FU alone was followed by a success rate of 87.1% and 72.2%, respectively. The cumulative probability of success after only trabeculectomy was 56% (p < 0.05). One case of hypotony maculopathy was found in the subgroup treated only with intraoperative MMC. CONCLUSIONS: This study confirms the effectiveness and relative safety of delayed post-operative 5-FU treatment in patients with clinical evidence of bleb failure. Only when OM had caused a lowering of IOP were late subconjunctival injections of 5-FU followed by good control of IOP. The use of intraoperative MMC may ensure a greater IOP decrease after OM.

Blue-on-yellow and achromatic perimetry in diabetic children without retinopathy.

OBJECTIVE: We compared blue-on-yellow perimetry with achromatic perimetry to determine whether the first was more sensitive in detecting visual field defects. RESEARCH DESIGN AND METHODS: We studied 50 children and adolescents (22 male, 28 female) with IDDM, ranging in age from 10.1 to 16.3 years (mean 13.3+/-2.1 years), with a disease duration of 5.2-10.0 years (mean 7.1+/-1.9 years). Patients were divided into subgroups according to the presence of persistent microalbuminuria. No one had signs of diabetic retinopathy when studied with fluorescein angiography. RESULTS: By achromatic perimetry, the analysis of subareas of the central 30 degrees of the visual field (0-9 degrees; 10-18 degrees; out of 18 degrees) showed no differences between diabetic subgroups in the central 18 degrees of the visual field, while a significant difference between the same subgroups was found outside the 18 degrees of the 24-2 program of the Humphrey perimeter (P = 0.027). By blue-on-yellow perimetry, in all three of the perimetric subareas evaluated, the sensitivity was lower in microalbuminuric patients than in normoalbuminuric ones. The differential sensitivity between the perimetric tests performed with blue-on-yellow and with achromatic stimuli showed statistically significant data, with a higher level of significance in the central 18 degrees (P < 0.0001) than outside the 18 degrees (P = 0.033). CONCLUSIONS: Our study suggests that blue-on-yellow perimetry is more useful and more sensitive than achromatic perimetry in the detection of preclinical visual field defects in diabetic children with microalbuminuria but without clinically detectable retinopathy.