Douglas S. Holsclaw

Epidemiology of ulcerative keratitis in Northern California

OBJECTIVE To determine the incidence and associated risk factors for ulcerative keratitis in northern California. METHODS In this large-population, retrospective, cohort study, all medical records with diagnosis coding for corneal ulcers during a consecutive 12-month period were reviewed. Incidence rates were calculated using a dynamic population model. Multivariate relative risk regression was conducted to evaluate potential risk factors for ulcerative keratitis. RESULTS Within the target population of 1 093 210 patients, 302 developed ulcerative keratitis. The incidence of ulcerative keratitis was 27.6 per 100 000 person-years (95% confidence interval, 24.6-30.9). The incidence of corneal ulceration in contact lens wearers was 130.4 per 100 000 person-years (95% confidence interval, 111.3-151.7), with an adjusted relative risk of 9.31 (7.42-11.7; P < .001) compared with non-contact lens wearers, who had an incidence of ulcerative keratitis of 14.0 per 100 000 person-years (11.7-16.6). Seven of 2944 people known to be infected with human immunodeficiency virus developed ulcerative keratitis, with 5 being contact lens wearers. The incidence of ulcerative keratitis in human immunodeficiency virus-positive patients was 238.1 per 100 000 person-years (95% confidence interval, 95.7-490.5), with an odds ratio of 9.31 (7.42-11.7; P < .001) compared with human immunodeficiency virus-negative patients, who had an incidence of ulcerative keratitis of 27.1 per 100 000 person-years (24.1-30.3). CONCLUSIONS The incidence of ulcerative keratitis in this population is higher than previously reported. This may be owing to the increasing prevalence of contact lens wear.

Pregnancy in patients with cystic fibrosis.

Abstract As more patients with cystic fibrosis reach adulthood, questions arise about the potential hazards of pregnancy. We reviewed the medical records of eight women with cystic fibrosis who had...

Supratarsal Injection of Corticosteroid in the Treatment of Refractory Vernal Keratoconjunctivitis

PURPOSE We studied supratarsal injection of corticosteroid as a new therapeutic modality for treating severe vernal keratoconjunctivitis to determine its efficacy in treating patients refractory to all conventional therapy. METHODS Twelve patients with vernal keratoconjunctivitis resistant to all established therapy were prospectively studied by randomly assigning them to receive supratarsal injection of either short- or intermediate-acting corticosteroid. Relief of symptoms and resolution of clinical signs were evaluated. Patients were followed up to four years to identify side effects. RESULTS All patients experienced dramatic symptomatic relief within one to five days, regardless of the type of corticosteroid injected. Marked decrease in cobblestone papillae was noted in 14.9 days (mean) after short-acting corticosteroid injection and 12.8 days after intermediate-acting corticosteroid injection (P = .65). Shield ulcers and limbal involvement resolved in one to three weeks, independent of the corticosteroid used (P = .90). No complications were observed with supratarsal injection of short-acting corticosteroid. One patient developed persistent increase of intraocular pressure after injection of intermediate-acting corticosteroid. CONCLUSIONS The dramatic symptomatic and clinical improvement suggests that supratarsal injection of corticosteroid may be a valuable therapeutic approach to treating refractory vernal keratoconjunctivitis. Short-acting and intermediate-acting corticosteroids were equally efficacious. Because of the lack of intraocular pressure increase observed with short-acting corticosteroid, we favor its use in supratarsal injection.

Inapparent transmission of Pseudomonas (Burkholderia) cepacia among patients with cystic fibrosis

Pseudomonas capacia is a significant pathogen in children and young adults with cystic fibrosis, and prevention of its acquisition has become an important goal in patient management. Although it is now clear that this bacterium can be transmitted from person to person, the frequency of this mode of acquisition and the measures required to prevent it are controversial. In this report we describe the use of a novel genotyping method to extend our previous investigation of person to person transmission of P. cepacia among patients with cystic fibrosis attending an educational program. Three (20%) of 15 individuals acquired P. cepacia after contact with a chronically colonized patient. Analysis revealed that the isolates recovered from the three newly colonized patients were the same as that from the index patient. We also demonstrated that pulmonary colonization with P. cepacia may not be detected by currently recommended culture methods for as long as 2 years after acquisition. These data indicate a need to develop more sensitive means of detecting P. cepacia colonization in order better to understand host-pathogen interaction and to optimize preventive strategies.

Congenital unilateral pulmonary venous atresia: definitive diagnosis and treatment.

Three cases of unilateral right-sided pulmonary venous atresia were evaluated over an 18-year period. These bring the total number of cases to 25 in the literature. The clinical presentation of all these patients was similar and consisted of recurrent pulmonary infections, asthma-like symptoms, and exercise intolerance. The patients presented in 1982 (patient 1, a 12-year-old boy), 1994 (patient 2, a 9-year-old girl), and 1999 (patient 3, a 13-year-old boy). All patients were evaluated with a chest roentgenogram, and patients 1 and 2 had a ventilation and perfusion scan. Patients 1 and 3 also had cardiac catheterization and pulmonary angiography. Patient 2 had a magnetic resonance imaging study of the chest. Only patient 3 had wedge pulmonary angiography. Although a rare congenital defect, this diagnosis should be strongly suspected based on the typical clinical presentation and the preliminary studies, such as the chest roentgenogram and ventilation and perfusion scan. However, for definitive diagnosis, cardiac catheterization with wedge pulmonary angiography is necessary. Anastomosis of the atretic pulmonary veins to the left atrium is a theoretical consideration. However, this may not be feasible due to pulmonary venous anatomy or significant pulmonary dysfunction with pulmonary vascular changes. In these circumstances, we recommend performing pneumonectomy to remove the nidus for repeated bouts of pulmonary infections, to eliminate the left-to-right shunt, and to eliminate the dead space contributing to exercise intolerance.

Cardiac function in patients with cystic fibrosis: evaluation by two-dimensional and Doppler echocardiography.

Two-dimensional and Doppler echocardiography were performed in 17 consecutive hospitalized patients with cystic fibrosis aged 6 to 38 years (mean 21 +/- 9) and in 10 normal subjects aged 24 +/- 7 years. Left ventricular and right ventricular ejection fraction were measured by a computerized light pen system and Simpsons rule from two-dimensional echocardiographic apical four and two chamber views. Right ventricular wall thickness, inferior vena cava size and the presence of tricuspid regurgitation by Doppler recording were also assessed. National Institutes of Health (NIH) score of clinical severity ranged from 22 to 72 (mean 51 +/- 15) (100 = excellent, 0 = poor). Four patients, all with an NIH score of 40 or less, died of respiratory failure within 1 year of the echocardiographic study. There was no significant difference between patients with cystic fibrosis and normal subjects with regard to right ventricular ejection fraction (59 +/- 11 versus 61 +/- 10%), left ventricular ejection fraction (67 +/- 8 versus 70 +/- 8%) and right ventricular systolic (5 +/- 1 versus 5 +/- 0.5 mm) and diastolic (2.4 +/- 0.5 versus 2.5 +/- 0.5 mm) wall thicknesses. A dilated inferior vena cava and mild tricuspid regurgitation by Doppler recording were detected in only one patient. A poor correlation was found between right ventricular ejection fraction and NIH clinical score (r = 0.26), chest X-ray score (r = 0.29) and pulmonary function tests. It is concluded that right and left ventricular systolic function is preserved in patients with moderately severe cystic fibrosis; clinical status in these patients is probably determined by the pulmonary rather than cardiac involvement.

A novel arginine substitution mutation in 1A domain and a novel 27 bp insertion mutation in 2B domain of keratin 12 gene associated with Meesmann’s corneal dystrophy

Aim: To determine the disease causing gene defects in two patients with Meesmann’s corneal dystrophy. Methods: Mutational analysis of domains 1A and 2B of the keratin 3 (K3) and keratin 12 (K12) genes from two patients with Meesmann’s corneal dystrophy was performed by polymerase chain reaction amplification and direct sequencing. Results: Novel mutations of the K12 gene were identified in both patients. In one patient a heterozygous point mutation (429A→C = Arg135Ser) was found in the 1A domain of the K12 gene. This mutation was confirmed by restriction digestion. In the second patient a heterozygous 27 bp duplication was found inserted in the 2B domain at nucleotide position 1222 (1222ins27) of the K12 gene. This mutation was confirmed by gel electrophoresis. The mutations were not present in unaffected controls. Conclusion: Novel K12 mutations were linked to Meesmann’s corneal dystrophy in two different patients. A missense mutation replacing a highly conserved arginine residue in the beginning of the helix initiation motif was found in one patient, and an insertion mutation, consisting of a duplication of 27 nucleotides, was found before the helix termination motif in the other.

Cyclosporine A 1% eye drops for the treatment of subepithelial infiltrates after adenoviral keratoconjunctivitis.

Purpose: To describe the use of cyclosporine A (CSA) 1% eye drops for the treatment of symptomatic corneal subepithelial infiltrates (SEI) occurring as a sequelae of adenoviral keratoconjunctivitis (AK) that are resistant to tapering of corticosteroid eye drops. Methods: This is a retrospective case series of patients seen at 2 institutions who had symptomatic corneal SEI occurring after AK that was resistant to tapering of corticosteroid eye drops and who were subsequently treated with CSA 1%. Information gathered included basic demographic information (age and sex), involved eye(s), duration of symptoms, initial best spectacle-corrected visual acuity (BSCVA), type of corticosteroid used, clinical course, and best spectacle-corrected visual acuity at the last follow-up visit. Results: Twelve eyes of 7 patients had symptomatic SEI develop after AK that were responsive to corticosteroid eye drops but were resistant to tapering. After the initiation of CSA eye drops, the corticosteroid eye drops could be tapered, and all eyes could be maintained on CSA eye drops once per day or less. Mean follow-up time was 13.0 months (range, 4-28 months). Conclusions: CSA eye drops may be an effective corticosteroid-sparing agent for the treatment of SEI after AK. The use of CSA in this setting warrants further study.

Cystic fibrosis-related diabetes is associated with HLA DQB1 alleles encoding Asp-57- molecules.

The incidence of insulin-dependent diabetes in individuals with cystic fibrosis is nearly 100 times greater than in the general population. In the latter group, strong associations with specific HLADQ/A1 andDQB1 alleles have been observed. To determine if a similar distribution of alleles occurs in cystic fibrosis patients with diabetes, a cohort of these individuals was typed forDQA1 andDQB1 alleles. HLADQB1*0201 (Asp57−) was more frequent in diabetics compared to controls (40.4 vs 28%), while the frequency of alleles encoding Asp57+ molecules was lower in diabetics relative to both the cystic fibrosisonly controls (P=0.025) and the general population (P=0.008). The presence of at least one protectiveDQA1-DQB1 heterodimer (i.e., Arg52− and Asp57+, respectively) in cis or trans was significantly lower in the diabetics than in either of the control groups. Thus, the HLA alleles known to be associated with insulindependent diabetes mellitus in the general population are also found in diabetics with cystic fibrosis.

Occult appendiceal abscess complicating cystic fibrosis

Three case histories illustrate the diagnostic dilemma encountered whenever a patient with CF who is receiving antibiotics is evaluated for abdominal pain. Although acute appendicitis with perforation and abscess formation is not a common complication of CF, it occurs more frequently than is generally appreciated. The large number of abdominal situations in CF which can cause pain confused with but not typical of acute appendicitis. The true underlying condition is further masked by the concurrent use of antibiotics for pulmonary infection. A higher index of suspicion is needed to rule out acute appendicitis in a patient with cystic fibrosis and abdominal pain. A greater awaremess of the possibility of occult appendiceal abscess may help to avoid this complication.