Pulmonary arteriovenous malformation and a concurrent patent ductus arteriosus in a Doberman.

A 7-week-old male Doberman presented with tachypnea, dyspnea and a VI/VI, left cranial, continuous heart murmur. Thoracic radiographs revealed severe left-sided cardiomegaly, presence of a rounded soft tissue opacity in the caudodorsal aspect of the thoracic cavity and signs of left-sided congestive heart failure. Clinical signs of heart failure were medically controlled. Echocardiography and computed tomography demonstrated a left-to-right shunting patent ductus arteriosus (PDA) in combination with a right-to-left shunting pulmonary arteriovenous malformation (PAVM) between the right main pulmonary artery and the right caudal pulmonary vein. Arterial blood gasses revealed mild hypoxemia. Transcatheter occlusion of the PDA using an Amplatz Canine Duct Occluder was performed. Four months post-operatively, echocardiography showed normal cardiac size and function with complete PDA closure. Thoracic radiographs revealed absence of the rounded opacity and resolution of cardiomegaly and vascular congestion. The PAVM was no longer visualized on repeated computed tomography and the arterial blood gasses were within normal limits. A PAVM connecting a pulmonary artery to a pulmonary vein has only rarely been reported in dogs. This report describes the presence of a congenital PAVM in combination with a PDA in a dog, which has not been previously reported in veterinary medicine.

Three-dimensional electroanatomical mapping for guidance of pulmonary vein isolation as treatment for persistent atrial fibrillation in a dog.

A two-year and four-month, male German Shepherd was referred for exercise intolerance and panting. Irregular heart auscultation (250 beats per minute (bpm)) and pulse deficits were noted on physical exam. Electrocardiogram (ECG) showed irregular, narrow-QRS tachycardia without P waves compatible with coarse atrial fibrillation (AF). A 24-h ECG showed sustained AF (mean ventricular response rate 92 bpm). Echocardiography showed no structural abnormalities. Given the young age and presence of AF-related symptoms, rhythm control was preferred. Transthoracic electrical cardioversion was successfully performed six weeks later but AF recurred within 24-h. Sotalol was started but discontinued due to poor tolerance and AF persisted. Seven months after AF diagnosis, radiofrequency catheter ablation (RFCA) aiming for pulmonary vein isolation was performed under general anaesthesia. After transseptal puncture, three-dimensional electroanatomical mapping of the left atrium was performed. Point-by-point pulmonary vein isolation was achieved by RFCA. Seventy-eight RFCA lesions were placed in the left atrium encircling the three pulmonary vein ostia followed by electrical cardioversion. No complications occurred and the dog was discharged with amiodarone. In the immediate post-operative phase, there was recurrence of persistent AF requiring electrical cardioversion. Furthermore, at one month after the ablation, the dog experienced a single and transient paroxysm of AF. Since then, stable sinus rhythm (SR) was retained on daily ECG monitoring at home and confirmed by 24-h ECG three months post-operatively. Amiodarone was stopped subsequently. At the time of writing (one year post-operative), the dog remains in SR with normal exercise tolerance.

Feasibility and safety of three-dimensional electroanatomical cardiac mapping, mapping-guided biopsy and transseptal puncture in dogs.

Three-dimensional electroanatomical mapping (3D EAM) has expanded radiofrequency catheter ablation applications in humans to almost all complex arrhythmias and has drastically reduced fluoroscopy use, yet its potential in dogs is poorly investigated. The objectives of the current study were to assess the feasibility and safety of 3D EAM of all four heart chambers, 3D EAM-guided biopsies and transseptal puncture in dogs. Eight healthy purpose-bred Beagle dogs. Electroanatomical mapping was performed under general anaesthesia during sinus rhythm using a 22-electrode mapping catheter. Left heart catheterisation was achieved by either retrograde transaortic access (n = 4) or transseptal puncture (n = 4). Successful 3D EAM of the right atrium and ventricle was achieved in all dogs at a median time of 33 (13-40) min and 17 (3-52) min, respectively. Left atrial and ventricular 3D EAM was successful in six and seven dogs, at a median time of 17 (4-27) min and 8 min (4-19 min), respectively. Complications requiring intervention occurred in one dog only and were a transient third degree atrioventricular block and pericardial effusion following transseptal puncture, which was treated by pericardiocentesis. All dogs recovered uneventfully. Fluoroscopy time was limited to a median of 7 min (0-45 min) and almost exclusively associated with transseptal puncture. Three-dimensional EAM of all cardiac chambers, including mapping-guided biopsy and transseptal puncture is feasible in small dogs. Complications are similar to those reported in human patients. This suggests a potential added value of 3D EAM to conventional electrophysiology in dogs with arrhythmias.

Serum hyaluronic acid, a marker for improved liver perfusion after gradual surgical attenuation of extrahepatic portosystemic shunt closure in dogs.

Current liver function tests used in dogs do not consistently normalise after successful surgical attenuation of portosystemic shunts (PSS). Serum hyaluronic acid (sHA) concentrations in dogs with PSS are reported to be higher at diagnosis than in healthy dogs. The objective of this study was to assess sHA as a marker of liver perfusion by measuring sHA concentrations in dogs before and after gradual surgical attenuation of extrahepatic (EH)PSS and by determining whether sHA concentrations could differentiate closed EHPSS from persistent shunting. Specificity of sHA was assessed by comparing sHA concentrations in dogs with EHPSS to those in dogs with other liver diseases. Twenty dogs with EHPSS had sHA concentrations measured at diagnosis, 1, 3, and 6 months postoperatively. In addition, sHA concentrations were determined in 10 dogs with other liver diseases. At EHPSS diagnosis, median sHA concentration was 335.6 ng/mL (43.0-790.7 ng/mL). All dogs had a significant decrease in sHA concentrations from 1 month postoperatively onwards (P < 0.05), regardless of surgical outcome. At all postoperative follow-up visits, there was a significant difference between the median sHA concentration in dogs with closed EHPSS vs. those with persistent shunting (P < 0.05). Median sHA concentration in dogs with other liver diseases was 89.8 ng/mL (22.9-160.0 ng/mL), which was significantly lower than dogs with EHPSS at diagnosis (P < 0.001). In conclusion, sHA is a promising non-invasive biomarker that can help to determine liver perfusion after surgical attenuation of EHPSS. In addition, sHA could potentially be used to differentiate dogs with EHPSS from dogs with other liver diseases.

Variability of serum concentrations of cystatin C and urinary retinol-binding protein, neutrophil gelatinase-associated lipocalin, immunoglobulin G, and C-reactive protein in dogs.

BACKGROUND: Markers of kidney dysfunction and damage have potential to detect chronic kidney disease (CKD) in early stages. However, data on long-term variation of these markers in healthy dogs is lacking and is crucial for the interpretation of results. HYPOTHESIS/OBJECTIVES: To determine temporal variations of serum cystatin C (sCysC) and urinary retinol-binding protein (uRBP), neutrophil gelatinase-associated lipocalin (uNGAL), immunoglobulin G (uIgG), and C-reactive protein (uCRP) in healthy dogs. ANIMALS: Eight clinically healthy adult Beagles were evaluated. METHODS: Longitudinal observational study. Serum cystatin C was determined by particle-enhanced nephelometric immunoassay. Urinary retinol-binding protein, uNGAL, uIgG and uCRP were determined by ELISA and concentrations were indexed to urinary creatinine. Within- and between-dog variance components (VC) and within-dog coefficients of variation (CV) were determined from blood and urine collected at eight time points over 1.5 years. RESULTS: Urinary C-reactive protein (uCRP) concentrations were consistently below the detection limit (5.28 ng/mL). Mean ± within-dog standard deviation for sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 ± 0.01 mg/L, 0.09 ± 0.03 mg/g, 2.32 ± 2.03 µg/g and 12.47 ± 10.98 mg/g, respectively. Within-dog CV for sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c exhibit a wide range of long-term within-dog variability. Researchers and veterinarians might need to take this into account when interpreting their results. To assess their diagnostic and predictive ability, future studies need to establish reference ranges for healthy dogs and dogs with CKD.

A single dose of intravenous combretastatin A4-phosphate is reasonably well tolerated and significantly reduces tumour vascularization in canine spontaneous cancers.

Combretastatin A4-phosphate (CA4P) is an anti-tumour vascular targeting agent which selectively blocks tumour blood flow. Research on CA4P in rodent tumour models is extensive; however, knowledge of its effect on spontaneous cancer is scarce. This study was conducted in canine patients with spontaneous solid tumours. The goal was to assess the toxicity and efficacy of CA4P in various spontaneous tumour types. Eight dogs with spontaneous tumours were enrolled and treated with a single dose of 75 mg m-2 intravenous CA4P. The dogs were screened and monitored before and after injection. Pre- and post-treatment tumour blood flow was analysed in vivo by power Doppler ultrasound (PDUS) and contrast-enhanced ultrasound (CEUS). Vessel destruction and tumour necrosis were evaluated by histopathology. Clinically relevant toxicity was limited to one case of temporary tetraparesis; other adverse events were mild. Significant cardiovascular changes were mostly confined to changes in heart rate and cTnI levels. Macroscopic tumour size reduction was evident in 2 dogs. Based on PDUS and CEUS, CA4P induced a significant decrease in vascular index and tumour blood flow. Post-treatment, histopathology revealed a significant increase of necrotic tumoural tissue and a significant reduction in microvessel density in tumoural tissue. Anti-vascular and necrotizing effects of CA4P were documented in a variety of canine spontaneous cancers with only minimal side effects. This is the first study reporting the administration of CA4P to canine cancer patients with in vivo and ex vivo assessment, and a first step toward implementing CA4P in combination therapies in veterinary oncology patients. The use of CA4P in canine patients was approved and registered by the Belgian Federal Agency for Medicines and Health Products (FAMHP) (approval number 0002588, registration number 6518 ID 2F12).

Contrast-Enhanced Ultrasound Examination for the Assessment of Renal Perfusion in Cats with Chronic Kidney Disease.

BACKGROUND: Contrast-enhanced ultrasound examination (CEUS) is a functional imaging technique allowing noninvasive assessment of tissue perfusion. Studies in humans show that the technique holds great potential to be used in the diagnosis of chronic kidney disease (CKD). However, data in veterinary medicine are currently lacking. OBJECTIVES: To evaluate renal perfusion using CEUS in cats with CKD. ANIMALS: Fourteen client-owned cats with CKD and 43 healthy control cats. METHODS: Prospective case-controlled clinical trial using CEUS to evaluate renal perfusion in cats with CKD compared to healthy control cats. Time-intensity curves were created, and perfusion parameters were calculated using off-line software. A linear mixed model was used to examine differences between perfusion parameters of cats with CKD and healthy cats. RESULTS: In cats with CKD, longer time to peak and shorter mean transit times were observed for the renal cortex. In contrast, a shorter time to peak and rise time were seen for the renal medulla. The findings for the renal cortex indicate decreased blood velocity and shorter total duration of enhancement, likely caused by increased vascular resistance in CKD. Increased blood velocity in the renal medulla has not been described before and may be because of a different response to regulatory factors in cortex and medulla. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrast-enhanced ultrasound examination was capable of detecting perfusion changes in cats with CKD. Further research is warranted to assess the diagnostic capabilities of CEUS in early stage of the disease process.

Evaluation of Renal Perfusion in Hyperthyroid Cats before and after Radioiodine Treatment.

BACKGROUND: Hyperthyroidism and chronic kidney disease (CKD) are common in elderly cats. Consequently, both diseases often occur concurrently. Furthermore, renal function is affected by thyroid status. Because changes in renal perfusion play an important role in functional renal changes in hyperthyroid cats, investigation of renal perfusion may provide novel insights. OBJECTIVES: To evaluate renal perfusion in hyperthyroid cats with contrast-enhanced ultrasound (CEUS). ANIMALS: A total of 42 hyperthyroid cats was included and evaluated before and 1 month after radioiodine treatment. METHODS: Prospective intrasubject clinical trial of contrast-enhanced ultrasound using a commercial contrast agent (SonoVue) to evaluate renal perfusion. Time-intensity curves were created, and perfusion parameters were calculated by off-line software. A linear mixed model was used to examine differences between pre- and post-treatment perfusion parameters. RESULTS: An increase in several time-related perfusion parameters was observed after radioiodine treatment, indicating a decreased blood velocity upon resolution of the hyperthyroid state. Furthermore, a small post-treatment decrease in peak enhancement was present in the renal medulla, suggesting a lower medullary blood volume. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrast-enhanced ultrasound indicated a higher cortical and medullary blood velocity and higher medullary blood volume in hyperthyroid cats before radioactive treatment in comparison with 1-month post-treatment control.

Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer.

Interleukin 12 (IL-12) is a powerful immunostimulatory cytokine with a strong antitumoural activity. In this work, the immunological, anti-angiogenic and clinical effects of three consecutive intratumoural IL-12 electrogene therapy (EGT) treatments were evaluated in nine dogs with spontaneous cancer. In all the dogs, tumour biopsies and blood samples were taken prior, during and after the intratumoural IL-12 EGT (on days 1, 8, 35 and 1, 3, 8, 15, 35, respectively). An initial decrease in immune cells was followed by an increase above baseline 1-3 weeks after treatment initiation. Interestingly, the decrease in peripheral leukocytes 2 days after the first intratumoural IL-12 EGT coincided with erythema and tumour swelling. Transient increases of IL-12 and interferon γ were measured in the serum and the tumour tissue, whereas IL-10 transiently increased only in the serum. The effect of intratumoural IL-12 EGT on the levels of IL-24 and vascular endothelial growth factor in the sera and tumour biopsies differed per dog. Via contrast-enhanced ultrasound (US) (on days 1, 8 and 35), we demonstrated that intratumoural IL-12 EGT resulted in a significant decrease of the relative blood volume and blood flow speed in the tumour compared with baseline. Metastases were present in two dogs. In one of these dogs, IL-12 EGT of the primary tumour caused a transient partial regression of the metastases, but not of the primary tumour. The second dog with metastases did not survive long enough to complete the entire treatment cycle. Despite encouraging immunostimulatory and anti-angiogenic effects after intratumoural IL-12 EGT, no clinically relevant outcomes were observed in this study, as persistent tumour regression could not be obtained. On the other hand, the laboratory and US results hold great promise for combinatorial strategies of intratumoural IL-12 EGT with conventional antitumour (immuno)therapies.

Description of the use of contrast-enhanced ultrasonography in four dogs with pancreatic tumours.

Canine pancreatic tumours are rare compared to human medicine and the detection and differentiation of pancreatic neoplasia is challenging with B-mode ultrasonography, which often leads to late clinical diagnosis and poor prognosis. This case report describes the findings of contrast-enhanced ultrasonography in four dogs with pancreatic adenocarcinoma or insulinoma. B-mode ultrasonography of the pancreas revealed a hypoechoic nodule in three dogs and heterogenous tissue in one dog. Contrast-enhanced ultrasonography was able to differentiate between two tumour types: adenocarcinomas showed hypoechoic and hypovascular lesions, whereas insulinomas showed uniformly hypervascular lesions. Contrast-enhanced ultrasonography findings were confirmed by cytology and/or histopathology. The results demonstrated that contrast-enhanced ultrasonography was able to establish different enhancement patterns between exocrine (adenocarcinoma) and endocrine (insulinoma) tumours in dogs.

Computed tomographic features of lesions detected in horses with tarsal lameness.

REASONS FOR PERFORMING STUDY: Tarsal pain is a common cause of hindlimb lameness in horses. Diagnosis can usually be made with radiography and ultrasonography; however, in some cases, these techniques are inconclusive and additional imaging is necessary. No studies describing computed tomography (CT) features of different tarsal lesions in horses with tarsal lameness are reported. OBJECTIVES: Our aims were as follows: 1) to characterise CT abnormalities in horses with tarsal lameness; 2) to compare CT findings with those from other imaging techniques; and 3) to assess whether CT can help to diagnose tarsal pathology. STUDY DESIGN: Retrospective case series. METHODS: Computed tomography of the tarsus was performed on 15 horses (n = 17 joints) with tarsal lameness. The horses were divided into 3 groups depending on the reason for CT examination, as follows: 1) other imaging techniques were inconclusive; 2) evaluation of a fracture; or 3) other imaging techniques showed tarsal lesions, and CT was performed to assess whether additional lesions were present. RESULTS: Group 1 included 7 horses. Lesions detected with CT included subchondral cyst-like lesions (2 horses); an osteolytic lesion in the cochlea tibiae (one horse); degenerative changes of the distal tarsal joints (2 horses); osteolytic lesions tarsometatarsal joint (one horse); and sclerosis of the third tarsal bone with a lesion of the tarsometatarsal interosseous ligament (one horse). In this group, CT provided information on the character and extent of the lesion that was not available with other imaging techniques. Computed tomography revealed more information about the extent and complexity of the fracture than radiography in Group 2, whereas CT did not provide extra information in Group 3. CONCLUSIONS: Focal lesions located between the tarsal bone surfaces are difficult or even impossible to detect with radiography and ultrasonography, but they can be detected and characterised with CT. POTENTIAL RELEVANCE: Computed tomography of the tarsus should be considered when radiography and ultrasonography are inconclusive, or for further evaluation of tarsal fractures.

On-chip quantum optics with quantum dot microcavities.

A novel concept for on-chip quantum optics using an internal electrically pumped microlaser is presented. The microlaser resonantly excites a quantum dot microcavity system operating in the weak coupling regime of cavity quantum electrodynamics. This work presents the first on-chip application of quantum dot microlasers, and also opens up new avenues for the integration of individual microcavity structures into larger photonic networks.

Management of focal limbal stem cell deficiency associated with soft contact lens wear.

PURPOSE: To present the varying manifestations of and the treatment methods for corneal epitheliopathies because of focal limbal stem cell deficiency (LSCD) associated with soft contact lens (SCL) wear. METHODS: The medical records of patients seen at 3 institutions who developed focal LSCD, based on clinical examination, that was attributed to SCL wear were reviewed. Information regarding the patients' demographics, contact lens wearing schedules, medical and surgical treatment modalities, and clinical and visual outcomes were recorded. RESULTS: Eighteen eyes of 10 SCL wearers were found to have varying degrees of corneal epitheliopathy secondary to focal LSCD. Nine of the 10 patients (90%) were women, and the mean age of all patients was 35.1 years (range, 20-58 years). The mean duration of SCL wear was 15.2 years (range, 4-30 years). Two patients wore the lenses for 20 hours per day. Mean follow-up time was 7.0 months (range, 0.25-24 months). Visual acuity at first examination was affected in 10 of the 18 eyes (55.6%) and ranged from 20/30 to hand motions. The focal LSCD was found superiorly in all involved eyes and inferiorly in only 5 of 18 eyes (27.8%). The epitheliopathy resolved or stabilized in 11 eyes (61.1%) with cessation of SCL wear and use of artificial tears. Five eyes required topical corticosteroid eyedrops, and 2 eyes required surgical intervention. One eye had a best spectacle-corrected visual acuity of less than 20/30 at last follow-up. CONCLUSIONS: Focal LSCD can be a result of SCL wear, presenting with varying manifestations. SCL wearers should be monitored routinely and counseled on this possible complication. Early identification of focal LSCD in SCL wearers with subsequent cessation of wear may prevent the need for surgical intervention.

Combined liver-kidney transplantation complicated by intraoperative discovery of a bronchobiliary fistula.

Herein, we report the case of an intraoperative diagnosis of bronchobiliary fistula during combined liver-kidney transplantation because of polycystic disease. The diagnosis necessitated changes in surgical and anesthesiologic management and in the overall medical decision-making process. Emergent isolation of the affected lung was instituted to mitigate a large air leak and ensure adequate respiratory exchange, and to enable surgical repair. The kidney transplantation procedure was delayed for a few hours, enabling hemodynamic and respiratory stabilization in the intensive care unit before conditions were deemed adequate to proceed. The posttransplantation course was complicated but eventually successful, and the patient recovered both liver and kidney function. At a later evaluation, we realized that diagnosis of bronchobiliary fistula could have been made preoperatively had the chest radiograph been interpreted correctly and had the clinicians involved had a higher degree of suspicion for this complication of polycystic liver disease.

Optical imaging of electrical carrier injection into individual InAs quantum dots.

We image the micro-electroluminescence (EL) spectra of self-assembled InAs quantum dots (QDs) embedded in the intrinsic region of a GaAs p-i-n diode and demonstrate optical detection of carrier injection into a single QD. Tunneling of electrons and holes into the QDs at bias voltages below the flat-band condition leads to a spectrum of sharp EL lines from a small number of bright spots on the diode surface, characteristic of emission from individual QDs. We explain this behavior in terms of Coulomb interaction effects and the selective excitation of a small number of QDs within the ensemble due to preferential tunneling paths for carriers.

Submonolayer quantum dots for high speed surface emitting lasers.

We report on progress in growth and applications of submonolayer (SML) quantum dots (QDs) in high-speed vertical-cavity surface-emitting lasers (VCSELs). SML deposition enables controlled formation of high density QD arrays with good size and shape uniformity. Further increase in excitonic absorption and gain is possible with vertical stacking of SML QDs using ultrathin spacer layers. Vertically correlated, tilted or anticorrelated arrangements of the SML islands are realized and allow QD strain and wavefunction engineering. Respectively, both TE and TM polarizations of the luminescence can be achieved in the edge-emission using the same constituting materials. SML QDs provide ultrahigh modal gain, reduced temperature depletion and gain saturation effects when used in active media in laser diodes. Temperature robustness up to 100 °C for 0.98 µm range vertical-cavity surface-emitting lasers (VCSELs) is realized in the continuous wave regime. An open eye 20 Gb/s operation with bit error rates better than 10-12has been achieved in a temperature range 25-85 °Cwithout current adjustment. Relaxation oscillations up to ∼30 GHz have been realized indicating feasibility of 40 Gb/s signal transmission.

Non-classical light emission from a single electrically driven quantum dot.

Easy to handle light sources with non-classical emission features are strongly demanded in the growing field of quantum communication. We report on single-photon emission from an electrically pumped quantum dot with unmatched spectral purity, making spatial or spectral filtering dispensable.

Intramuscular aripiprazole or haloperidol and transition to oral therapy in patients with agitation associated with schizophrenia: sub-analysis of a double-blind study.

OBJECTIVE: A sub-population analysis of 325 patients with agitation (Positive and Negative Syndrome Scale Excited Component [PEC] score > or = 15 and < or = 32; score of > or = 4 on > or = 2 items) associated with schizophrenia in a randomized, double-blind study investigating the efficacy and tolerability of intramuscular (IM) aripiprazole 9.75 mg, IM haloperidol 6.5 mg, or IM placebo and the transition to oral therapy. RESEARCH DESIGN AND METHODS: Over 24 h, patients could receive up to three IM injections; the second and third administered > or = 2 and > or = 4 h, respectively, after the first, if deemed clinically necessary. Following IM treatment, oral aripiprazole or haloperidol was administered for 4 days. The primary efficacy measure was the mean change in PEC score from baseline at 2 h. RESULTS: At 2 h, mean improvements in PEC scores with IM aripiprazole (-8.0) were significantly greater versus IM placebo (-5.7; p < or = 0.01), and similar versus IM haloperidol (-8.3). Secondary efficacy measures also significantly improved with active IM treatment versus IM placebo. Continuation with oral treatment provided continued efficacy with both active treatments. The safety profiles of IM and oral aripiprazole were similar. The incidence of extrapyramidal symptom-related adverse events was 0% with IM aripiprazole, 1.6% with IM placebo and 16.5% with IM haloperidol. CONCLUSION: Intramuscular aripiprazole is effective in patients with acute agitation associated with schizophrenia, comparable to IM haloperidol, and enables convenient transfer to oral aripiprazole therapy.

Linkage mapping of Thiel-Behnke corneal dystrophy (CDB2) to chromosome 10q23-q24.

Corneal dystrophy of the anterior basement membrane is a heterogeneous set of diseases characterized by painful, recurrent, bilateral erosions of the cornea, which often result in significant visual impairment. There are several similar but clinically distinct forms of anterior basement membrane/Bowman's membrane disease, including two autosomal dominant forms, Reis-Bücklers and Thiel-Behnke corneal dystrophy. Genes causing autosomal, nonsyndromic corneal dystrophy have been mapped to human chromosomes 1p, 5q, 12q, 16q, 17p, and 20p. Using microsatellite markers closely linked to the known corneal dystrophy loci, we excluded linkage between the known sites and the disease locus in a large, four-generation family with Thiel-Behnke corneal dystrophy. A genome-wide search using a panel of microsatellite markers demonstrated a maximum two-point lod score of 4.0 at 0% recombination between the disease locus in this family and the marker D10S1239, which maps to 10q23-q24. Testing with additional microsatellite markers from 10q places the disease locus between D10S677 and D10S1671, a distance of approximately 12.0 cM, with a maximum multipoint lod score of 5.5. Based on this evidence, we have identified another locus (CDB2) for corneal dystrophy of the anterior basement membrane/Bowman's membrane, Thiel-Behnke type, further demonstrating the exceptional genetic and phenotypic heterogeneity of these diseases.