Severity of medial meniscus damage in the canine knee after anterior cruciate ligament transection.

OBJECTIVE: To examine the relationship between the severity of cartilage damage and the severity of meniscus damage after transection of the anterior cruciate ligament (ACLT) in adult dogs. DESIGN: Data were obtained from 40 dogs which underwent ACLT and from three additional sham-operated dogs that were subjected to arthrotomy but not ligament transection. Joint pathology was analysed 12, 24 or 32 weeks after surgery. The severity of damage to the articular cartilage on the femoral condyle and tibial plateau was graded with a scoring system based on that of the Sociètè Française d'Arthroscopie and meniscus damage was graded on a 0-4 scale. RESULTS: No damage to the meniscus or articular cartilage was observed 12 weeks after surgery in the dogs subjected only to arthrotomy. In contrast, tears of the medial meniscus were observed in two of 10 (20%) dogs examined 12 weeks after ACLT. The incidence of severe tears increased to 86% and 84% after 24 weeks and 32 weeks, respectively. Damage to the lateral meniscus was mild, with only 7.5% of all dogs with a cruciate-deficient knee having a bucket handle or complete tear. Most of the unstable knees exhibited ulceration of the articular cartilage of the femoral condyles and tibial plateaus 12 weeks (mean chondropathy score+/-standard deviation 11.9+/-8.5, N=10), 24 weeks (7.9+/-5.0, N=7), and 32 weeks (7.1+/-5.5, N=23) after ACLT. The mean chondropathy scores for the tibial plateaus were similar to those for the femoral condyles. No correlation was apparent between the severity of cartilage damage and of meniscus damage for either joint surface. CONCLUSION: Damage to the medial meniscus is a consistent feature of the pathology which develops in the canine knee after ACLT, but the severity of cartilage damage is not correlated with the severity of meniscal damage.

Effect of intraarticular hyaluronan injection on synovial fluid hyaluronan in the early stage of canine post-traumatic osteoarthritis.

OBJECTIVE: To determine how the quantity and molecular weight of synovial fluid hyaluronan (HA) within the synovial fluid (SF) of osteoarthritis (OA) joints is affected by intraarticular injection of HA. METHODS: Dogs in which OA was induced by transection of the anterior cruciate ligament received 5 weekly injections of HA (1.5 x 10(6) Da) in saline (10 mg/0.67 ml) or an equal volume of saline into the operated knee, beginning the day after surgery. Immediately before each injection, SF was aspirated and the volume of SF and the concentration of HA was measured (uronic acid), and the molecular weight of the HA in each sample was estimated by electrophoresis in agarose. RESULTS: The volume of SF in the unstable knee increased after surgery, and the molecular weight decreased from approximately 2.5 x 10(6) Da to approximately 2 x 10(6) Da. Injection of HA did not affect the volume of SF or average molecular weight of HA in samples obtained immediately before each injection or at the end of the experiment, 12 weeks after surgery. The SF HA concentration fell from a baseline value of 2.3 +/- 0.1 mg/ml to 1.1 +/- 0.2 mg/ml the day after surgery and remained low throughout the course of injections. The HA concentration 12 weeks after surgery in the HA injected knees was approximately 40% lower than the preoperative value, although it increased slightly relative to saline injected knees (1.4 +/- 0.3 vs 1.1 +/- 0.01 mg/ml, respectively; p = 0.04). CONCLUSION: Intraarticular injection of HA did not alter the volume of SF or molecular weight of HA in SF of OA canine knees, nor did it restore the HA concentration to that of normal canine SF.

Synovial fluid glycosaminoglycan concentration does not correlate with severity of chondropathy or predict progression of osteoarthritis in a canine cruciate deficiency model.

OBJECTIVE: Considerable interest exists today in biochemical or immunochemical tests for monitoring the progression of osteoarthritis (OA). It has been suggested that measurements made on synovial fluid (SF) will more accurately reflect the magnitude of cartilage destruction in an index joint than those performed on serum. However, we have shown that the synovitis that occurs in OA affects the rate of protein clearance from the joint. We tested the hypothesis that if adjusted for clearance rate, the SF concentration of cartilage proteoglycans (PG) estimates severity of chondropathy and predicts progression of cartilage damage more accurately than if clearance is not taken into account. METHODS: Clearance of radioiodinated serum albumin (RISA), a surrogate for the clearance of PG, was measured in 19 adult dogs at baseline and again 16 weeks and 32 weeks after anterior cruciate ligament transection (ACLT). Severity of chondropathy was determined arthroscopically after 16 weeks of instability and at postmortem 32 weeks after ACLT. RESULTS: Adjustment for the RISA clearance rate showed that the SF PG concentration markedly underestimated the quantity of PG released from the OA cartilage. Regardless of whether the concentration was adjusted for clearance, no correlation existed between the SF PG level and the severity of chondropathy. Further, the SF concentration of PG 16 weeks after ACLT failed to predict severity of cartilage damage at postmortem. CONCLUSION: SF concentration of a cartilage derived molecule is unlikely to predict the course of cartilage damage in an OA joint over time or in response to treatment with a potential disease modifying OA drug.

The role of analgesics in the management of osteoarthritis pain.

Osteoarthritis (OA), previously called degenerative joint disease, is a common condition. Figures from the United States indicate that as many as 80% of the population has radiographic evidence of this disease by the age of 65 years, and difficulty with ambulation, mostly attributable to OA, accounts for as many as 30% of all visits to a doctor. There is no known cure for OA and hence treatments are used to reduce pain and other symptoms, maintain and/or improve joint mobility, and limit functional disability, with the overall management goal of improving the patients' quality of life. To this point, one of the key objectives of treatment is to manage knee pain. In the past, treatment was most often initiated with the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs). However, evidence that (1) NSAIDs offer no additional symptomatic benefit over simple analgesics, such as paracetamol (acetaminophen), for many patients with OA, (2) NSAID-related adverse gastrointestinal (GI) effects are a significant cause or morbidity and mortality, and (3) NSAIDs could have a possible deleterious effect on articular cartilage metabolism, has led to a change in management strategy. Contemporary thinking is that nonpharmacologic measures should be tried first, with pharmacologic intervention used as an adjunct. Nonpharmacologic therapy includes such things as patient education, weight loss, physical therapy, occupational therapy, and exercise. Paracetamol, in doses of as high as 4000 mg/day, is the first-line drug of choice for the management of the pain of OA. If the patient does not respond to paracetamol, NSAIDs may be an appropriate alternative, provided they are not medically contraindicated. Because of their GI toxicity, it is suggested that NSAIDs be used in the lowest possible dose for the shortest possible time. In OA, the intensity of pain varies both during the day and night, enabling the use of NSAIDs with a short half-life on an as-needed basis. Strategies to reduce the risk of NSAID-related GI complications include prophylaxis with misoprostol. Current developments in the field of OA management are also discussed, including the emergence of drugs that specifically inhibit cyclooxygenase 2 (COX-2) and disease-modifying treatments.

Effects of a bisphosphonate on bone histomorphometry and dynamics in the canine cruciate deficiency model of osteoarthritis.

OBJECTIVE: To examine the effect of the bisphosphonate NE- 10035 on bone histomorphometry and bone dynamics in dogs after transection of the anterior cruciate ligament (ACL), and to determine, in a placebo controlled trial, whether treatment modified the severity of pathologic changes of osteoarthritis (OA) in the unstable joint. METHODS: Ten adult male mongrel dogs underwent ipsilateral ACL transection. Five dogs then received daily subcutaneous injections of NE-10035 on 5 days per week for 12 weeks beginning the day after surgery. The other 5 dogs served as concurrent OA controls and received subcutaneous injections of saline on the same schedule. At sacrifice, 12 weeks after ACL transection, the articular cartilage and synovium of both knees of each dog were evaluated grossly and histologically and the water content and uronic acid concentration of the articular cartilage was determined. Fifteen days before sacrifice, each dog was injected with the fluorochrome label calcein. The injection regimen was repeated 10 days after the initial date. At sacrifice, static and dynamic variables of bone formation were assessed and bone resorption was quantified. RESULTS: In the OA knee of the control group, bone formation and resorption were markedly increased. NE-10035 markedly reduced both formation and resorption of cancellous subchondral bone, but had no effect on osteophyte formation or pathologic changes of OA in the articular cartilage, which were mild in both treatment groups. Water content of the OA cartilage was increased by about 8% in both treatment groups. However, among the controls, the mean uronic acid concentration of the OA cartilage was increased by about 30% in comparison with values for the contralateral knee, while in the NE-10035 treatment group the mean uronic acid concentration of OA knee cartilage was about 15% lower in the active treatment group than in cartilage from the contralateral knee (p = 0.003 for the difference in OA knee uronic acid concentration between the 2 treatment groups, relative to that in the contralateral knee). CONCLUSION: The antiresorptive agent employed in this study effectively reduced turnover of subchondral bone in the OA joint, consistent with the coupling of bone formation to bone resorption at that site. Nonetheless, over the 12 week period of the study it had no effect on osteophyte formation, in which bone formation occurs via enchondral ossification and is not linked to bone resorption, and, despite the clear inhibition of bone turnover in the OA knee of the active treatment group, did not affect the severity of cartilage changes of OA. It should be noted, however, that although treatment with this antiresorptive agent did not affect the level of chondropathy, the cartilage changes in both treatment groups were relatively mild and the sample size relatively small. Additional studies with a larger number of animals and a longer period of observation (to increase the severity of pathology) are warranted to determine whether the inhibition of bone turnover and the decrease in proteoglycan concentration that resulted from therapy will affect articular cartilage degeneration in the OA joint.

Diacerhein treatment reduces the severity of osteoarthritis in the canine cruciate-deficiency model of osteoarthritis.

OBJECTIVE: To determine if diacerhein protects against the early stages of joint damage in a canine model of osteoarthritis (OA). METHODS: OA was induced in 20 adult mongrel dogs by transection of the anterior cruciate ligament of the left knee. Beginning the day after surgery, dogs in the active treatment group were dosed twice a day with capsules of diacerhein, providing a total daily dose of 40 mg/kg, for 32 weeks. Dogs in the control group received placebo capsules on the same schedule. Pathology in the unstable knee was assessed arthroscopically 16 weeks after surgery and by direct observation when the dogs were killed 32 weeks after surgery. The severity of gross joint pathology was recorded, and samples of the medial femoral condyle cartilage and the synovial tissue adjacent to the central portion of the medial meniscus were collected for histologic evaluation. Water content and uronic acid concentration of the articular cartilage from the femoral condyle were determined, and collagenolytic activity in extracts of cartilage pooled from the medial and lateral tibial plateaus was assayed against 14C-labeled collagen fibers. RESULTS: Diacerhein treatment slowed the progression of OA, as measured by grading of gross changes in the unstable knee at arthroscopy 16 weeks after cruciate ligament transection (P = 0.04) and at the time the animals were killed, 32 weeks after surgery (P = 0.05). However, 32 weeks after ACL transection, the mean proteoglycan concentration and water content of the OA cartilage and the level of collagenolytic activity in extracts of the cartilage were not significantly different in the diacerhein treatment group than in the placebo treatment group. CONCLUSION: Diacerhein treatment significantly reduced the severity of morphologic changes of OA compared with placebo. These findings support the view that diacerhein may be a disease-modifying drug for OA.

Effect of intraarticular hyaluronan injection in experimental canine osteoarthritis.

OBJECTIVE: To determine if intraarticular injections of hyaluronan (HA) protect against the early stages of joint damage in a canine model of osteoarthritis (OA). METHODS: OA was induced in adult mongrel dogs by transection of the anterior cruciate ligament of the left knee. One group of dogs (n=7) was treated with 5 weekly injections of HA (MW 1,500,000) into the operated knee beginning 1 day after ligament transection. The control group (n=6) was injected with saline on the same schedule. Twelve weeks after surgery, all dogs were killed, the severity of pathologic changes of OA was graded, and composition of the cartilage and extent of aggregation of proteoglycans (PGs) synthesized in vitro by cartilage slices were determined. RESULTS: All dogs showed gross morphologic changes typical of OA in the unstable knee. The severity of joint pathology in HA-treated dogs was comparable with that in the saline-injected controls. In OA cartilage from the saline-treated group, the mean uronic acid concentration was 30-60% greater than that in the contralateral knee. In sharp contrast, the uronic acid concentration in OA cartilage from the HA-treated dogs was 10-30% lower than that in cartilage from the contralateral knee (P=0.02 and P=0.03, respectively, for samples from the medial and lateral femoral condyle). The extent of aggregation of PG synthesized in vitro by cartilage from HA-injected animals was similar to that synthesized by cartilage from the saline-injected dogs. CONCLUSION: In this canine model of OA, the series of intraarticular injections of HA did not alter development of osteophytosis or fibrillation. However, the PG concentration of cartilage in the OA knee was significantly reduced by this treatment, suggesting that HA therapy might adversely affect the biomechanical properties of the cartilage.

Oral administration of doxycycline reduces collagenase and gelatinase activities in extracts of human osteoarthritic cartilage.

OBJECTIVE: To determine whether oral administration of doxycycline in clinically relevant doses will suppress activities of collagenase and gelatinase in extracts of human osteoarthritic (OA) cartilage. METHODS: Femoral heads were obtained from 21 patients undergoing arthroplasty for endstage hip OA. Activities of collagenase and gelatinase were measured in extracts of the OA cartilage from patients who received doxycycline, 100 mg bid or qam for 5 days before surgery (n = 5 and n = 6, respectively), 200 mg as a single dose 3 days before surgery (n = 4); or no doxycycline (n = 6). RESULTS: Five days of doxycycline treatment, in a dose of either 100 mg bid or 100 mg qam, inhibited gelatinase activity in the cartilage extracts (p = 0.003, 0.008, respectively). The bid dose also inhibited collagenase activity (p = 0.002), but inhibition of collagenase with 100 mg qam did not quite reach statistical significance (p = 0.055), in comparison with the values for the untreated OA controls. The single 200 mg dose, given 3 days before procurement of the cartilage, was ineffective in inhibiting metalloproteinase activity. CONCLUSION: Oral administration of doxycycline significantly inhibited collagenase and gelatinase activity in human OA cartilage. The effective dose is likely to be well tolerated during chronic administration, e.g., in a clinical trial to assess the potential of the drug to modify cartilage breakdown in OA.

Periosteal new bone formation in a canine neuropathic model of osteoarthritis.

OBJECTIVE: To characterize, for the first time, periosteal new bone formation in a well-established canine model of accelerated osteoarthritis (OA) with features of neuropathic arthropathy. METHODS: Seven dogs underwent left L4-S1 dorsal root ganglionectomy (DRG), followed 3 weeks later by transection of the anterior cruciate ligament of the ipsilateral knee (ACLT). Eight weeks thereafter, a postmortem examination was performed to assess the severity of cartilage changes of OA and the formation of new bone on the distal femur and proximal tibia in the cruciate-deficient limb. RESULTS: As described previously, extensive full-thickness ulceration of the articular cartilage was present in the unstable knee of every dog. The femoral shaft immediately proximal to the condyles in the unstable limb was consistently wider (mean +/- SD diameter 22.4 +/- 2.2 mm) than that in the contralateral limb (19.9 +/- 1.3 mm; P = 0.01). Xeroradiography and histologic examination of the distal femur revealed extensive formation of woven bone on the periosteal surfaces of the medial, lateral, and anterior aspects of the femoral shaft in the OA limb of every dog. These bony changes were not seen in radiographs of dogs that underwent DRG with the cruciate ligament left intact (n = 8) or of neurologically intact dogs that underwent ACLT (n = 7) and were examined 24 weeks after surgery. CONCLUSION: Formation of new periosteal bone on the distal femur and tibia is a feature of this model of accelerated OA that is not seen in the conventional ACLT model of OA in the neurologically intact dog. This observation suggests that interruption of sensory input from the limb may affect the regulation of osteogenesis in the mechanically unstable joint.

Serial kinematic analysis of the canine hindlimb joints after deafferentation and anterior cruciate ligament transection.

OBJECTIVE AND DESIGN: Transection of the anterior cruciate ligament 2 weeks after ipsilateral hindlimb deafferentation leads to osteoarthritis of the knee joint within 3 weeks. We analyzed the gait of six dogs that underwent this procedure in order to identify kinematic changes that could account for this rapid joint degeneration. All animals were video taped, 1, 3, 6, 9 and 13 weeks after surgery while they trotted on a treadmill. RESULTS: In each dog, extension of the hip, knee and ankle joints of the unstable limb was increased, and the yield phase of the unstable knee was delayed or attenuated. When killed, five of six dogs showed a large full-thickness cartilage ulcer on the distal and/or anterior surface of the medial femoral condyle of the unstable knee; in the sixth dog, a smaller ulcer was observed. However, the severity of pathology in each individual was not obviously related to difference among the dogs in postoperative joint kinematics. CONCLUSIONS: These data, and results of prior studies in humans and dogs, suggest that knee hyperextension resulting from limb deafferentation, and knee instability resulting from anterior cruciate ligament transection, operate in concert to create a mechanical environment (i.e., increased tibiofemoral separation and changes in the loading of articular surfaces) that results in rapid joint breakdown.

Effects of diacerhein in an accelerated canine model of osteoarthritis.

OBJECT: To determine whether diacerhein has a disease-modifying effect in an accelerated canine model of osteoarthritis. DESIGN: Fourteen adult mongrel dogs underwent unilateral L4-S1 dorsal root ganglionectomy (DRG), followed 3 weeks later by ipsilateral anterior cruciate ligament transection. Seven dogs received diacerhein (15-20 mg/kg) daily throughout the interval between DRG and sacrifice, eight weeks after ligament transection. The other seven dogs served as OA controls. RESULTS: The mean volume of synovial fluid obtained from the OA knee of the diacerhein-treated dogs was approximately 40% less than that from the OA knee of the controls. In addition, diacerhein appeared to reduce the severity of fibrillation (femoral condyle) and full-thickness ulceration (trochlear ridge) of the articular cartilage and the level of collagenase activity in extracts of the OA cartilage, and to increase net PG synthesis in the OA cartilage, although none of the above changes were statistically significant. CONCLUSION: The differences between the diacerhein group and untreated OA controls, even though not statistically significant, suggest that diacerhein was active in this rapidly progressive model of OA. Because changes associated with initiation of OA may be different than those associated with progression, whether diacerhein has a disease-modifying effect should be examined in a less rapidly progressive model.

Effects of oral doxycycline administration on histomorphometry and dynamics of subchondral bone in a canine model of osteoarthritis.

OBJECTIVE: To determine whether oral administration of doxycycline, in a dose that inhibits cartilage breakdown in a canine cruciate deficiency model of osteoarthritis (OA), affected formation or resorption of subchondral bone. METHODS: Ten healthy adult mongrel dogs underwent transection of the left anterior cruciate ligament. Five were given doxycycline, 3.5 mg/kg/day, orally, from the day after surgery until they were sacrificed 6 weeks later; the other 5 dogs served as positive OA controls. Three weeks before sacrifice, each dog was given an intravenous injection of the fluorochrome label, calcein, on each of 2 consecutive days; 10 days later, the injection regimen was repeated. At sacrifice, samples of bone from the medial femoral condyle of both knees of each dog were obtained for staining with Villanueva tetrachrome to localize the fluorochrome label and McNeal's tetrachrome for measurement of osteoid and cell counts. RESULTS: Cruciate deficiency resulted in a marked decrease in bone mass, with increased osteoclastic activity and increased bone formation. Doxycycline treatment did not significantly affect either bone formation or bone resorption. CONCLUSION: Doxycycline protects against joint breakdown in this OA model via inhibition of matrix metalloproteinases in articular cartilage, rather than through an effect on subchondral bone.

A whole-cell Candida albicans assay for the detection of inhibitors towards fungal cell wall synthesis and assembly.

A whole-cell C. albicans screen was designed to identify novel inhibitors interacting with the synthesis, assembly and regulation of the fungal cell wall. C. albicans was grown in a paired broth assay in 96-well plates with natural product extracts or pure chemical compounds in the presence and absence of the osmotic stabilizer, sorbitol. Growth was visually examined over a 7-day period and scored into different growth categories. Positives from the sorbitol rescue were then examined under the microscope for morphological alterations and grouped into several morphological classes. Sorbitol protection and cell morphology were indicators of novel antifungal agents from natural product extracts and pure compounds.

Experimental assessment by high frequency ultrasound of articular cartilage thickness and osteoarthritic changes.

OBJECTIVE: Osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the involved joint. Accurate, reproducible measurement of the thickness of the cartilage in vivo, however, is difficult. Because development of an ultrasonic imaging device for intraarticular use is feasible and would permit acquisition of information that could complement the assessment of articular cartilage made at arthroscopy, we evaluated the efficacy of high frequency ultrasound in assessing the thickness and subsurface characteristics of normal and OA cartilage. METHODS: Blocks of human femoral cartilage and subchondral bone and chips of cartilage alone were examined in vitro with an experimental 25 MHz pulse-echo ultrasound scanner that portrayed cross sections of the cartilage as B-mode images. The gross and histologic appearance of the articular surface was used to identify specimens of unblemished, normal cartilage and OA cartilage. The speed of sound in cartilage, determined from measurements of cartilage thickness and sound transmission, was related to its biochemical composition. RESULTS: The speed of sound in normal cartilage (1658 +/- 185 m/s, n = 27) was greater than that in OA cartilage (1581 +/- 148 m/s, n = 40, p = 0.06), but was not related to the cartilage water content or the concentration of uronic acid or hydroxyproline. Images of normal cartilage showed a smooth echo band at the tissue surface with a hypoechoic matrix; in scans of fibrillated cartilage the width of this band was proportional to the depth of fibrillation (r = 0.78). Ultrasonic and histologic measurements of OA cartilage thickness were closely correlated (r = 0.87) and the mean coefficient of variation for repeated measurements was 2%. CONCLUSION: High frequency ultrasonic images obtained in vitro provide highly accurate and reproducible measurements of the thickness and subsurface characteristics of normal and OA articular cartilage.

A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis.

OBJECTIVE: We evaluated the effectiveness and rapidity of onset of S-adenosylmethionine (SAM), administered as daily intravenous boluses of 400 mg for 5 days, followed by oral tablets, 200 mg thrice daily for 23 days, versus a matching placebo regimen, in the treatment of 81 patients with symptomatic knee osteoarthritis (OA). METHODS: The study was bicentric, randomized, double blinded, and placebo controlled. Patients underwent a 7-day washout of arthritis medications prior to initiation of this study treatment. Major outcome measures were the Stanford Health Assessment Questionnaire disability and pain scales, and supplemental visual analog scales for rest and walking pain. RESULTS: At one site, patients had milder OA, the baseline characteristics of the treatment groups were well matched, and the SAM treated group showed significantly greater reduction in overall pain and rest pain (p < 0.05) than the placebo treated group. At the other site, the patients had more severe OA, randomization yielded markedly different treatment groups, and the response to treatment did not differ between groups. Onset of SAM effect was seen as early as 14 days after the start of treatment. CONCLUSION: SAM may be an effective treatment for some patients with symptomatic knee OA, and merits further study. Intravenous loading before oral maintenance therapy may be advantageous.

Serial kinematic analysis of the unstable knee after transection of the anterior cruciate ligament: temporal and angular changes in a canine model of osteoarthritis.

Transection of the anterior cruciate ligament in the dog leads to osteoarthritis. This study defines the kinematic changes in the unstable knee after transection of the cruciate ligament (six dogs) and after a sham operation (four dogs). In the dogs that were anterior cruciate ligament-deficient (ACL-D), the duration of stance 1 week postoperatively decreased 38% from the preoperative value, but only a 4% decrease was seen at 6 weeks. The duration of double hindlimb support increased from 6 to 19% of the entire cycle 1 week after surgery but returned to the baseline value by 18 weeks. As the unstable limb contacted the treadmill belt, the initial flexion (yield) and subsequent extension (propulsive) phases were not evident or were markedly attenuated in every ACL-D dog throughout the 26-week period of observation. The angular velocity patterns were characterized by a slight extension velocity at touchdown (compared with a zero value preoperatively) and a decrease in the peak velocities (both flexion and extension) during the remainder of the stance phase. None of these changes was observed in the animals that had a sham operation. These data indicate that, in the dog, the nervous system compensates for instability of the knee by altering angular, but not temporal, parameters. The extension velocity at touchdown and the reduction in peak flexion velocity during the yield component of the stance phase may reduce the ability of the limb to absorb impact forces and lead to the development of osteoarthritis of the knee.(ABSTRACT TRUNCATED AT 250 WORDS)

Current practices for monitoring ocular toxicity related to hydroxychloroquine (Plaquenil) therapy.

OBJECTIVE: Growing interest in aggressive early management of rheumatoid arthritis (RA) with hydroxychloroquine (alone or in combination with other immunomodulating drugs) is reason to review current practices for monitoring ocular toxicity in patients who take antimalarial therapy. METHODS: We surveyed by mail all ophthalmologists and rheumatologists in the State of Indiana about their practices in this regard. RESULTS: Twenty-nine of 31 rheumatologists (94%) responded. All but one recommended ophthalmologic examinations every 6 months and 41% would leave the choice of testing procedures to the ophthalmologist. Fifty percent had discontinued hydroxychloroquine because of a patient's failure to make and/or keep an appointment with the ophthalmologist. Of 213 ophthalmologists surveyed, 150 (70%) responded. Seventy-nine percent recommended semiannual examinations. Funduscopy, visual acuity, and color vision tests were reported to be performed routinely. Eleven of 13 retina specialists (85%), but only 25% of 127 general ophthalmologists, would obtain macular photographs (p < 0.001). Forty-two percent of general ophthalmologists, compared with 8% of retina specialists, would perform computerized perimetry (p < 0.001). Recognition of retinal hyperpigmentation as a classic sign was surprisingly low in both groups. Concurrent review of the medical records of 24 patients with RA or systemic lupus erythematosus showed extremely variable followup intervals for ophthalmologic examination; 7 of the 24 patients had no record of an ophthalmologic evaluation. CONCLUSION: As interest in the early, aggressive management of RA continues to grow, significant education needs to be devoted to the monitoring and diagnosis of ocular toxicity of hydroxychloroquine by both rheumatologists and ophthalmologists.