A Consensus Statement on the Terminology for Automated Visual Field Abnormalities.

BACKGROUND: A multitude of terms have been used to describe automated visual field abnormalities. To date, there is no universally accepted system of definitions or guidelines. Variability among clinicians creates the risk of miscommunication and the compromise of patient care. The purposes of this study were to 1) assess the degree of consistency among a group of neuro-ophthalmologists in the description of visual field abnormalities and 2) to create a consensus statement with standardized terminology and definitions. METHODS: In phase one of the study, all neuro-ophthalmologists in Israel were asked to complete a survey in which they described the abnormalities in 10 selected automated visual field tests. In phase 2 of the study, the authors created a national consensus statement on the terminology and definitions for visual field abnormalities using a modified Delphi method. In phase 3, the neuro-ophthalmologists were asked to repeat the initial survey of the 10 visual fields using the consensus statement to formulate their answers. RESULTS: Twenty-six neuro-ophthalmologists participated in the initial survey. On average, there were 7.5 unique descriptions for each of the visual fields (SD 3.17), a description of only the location in 24.6% (SD 0.19), and an undecided response in 6.15% (SD 4.13). Twenty-two neuro-ophthalmologists participated in the creation of a consensus statement which included 24 types of abnormalities with specific definitions. Twenty-three neuro-ophthalmologists repeated the survey using the consensus statement. On average, in the repeated survey, there were 5.9 unique descriptions for each of the visual fields (SD 1.79), a description of only the location in 0.004% (SD 0.01), and an undecided response in 3.07% (SD 2.11%). Relative to the first survey, there was a significant improvement in the use of specific and decisive terminology. CONCLUSIONS: The study confirmed a great degree of variability in the use of terminology to describe automated visual field abnormalities. The creation of a consensus statement was associated with improved use of specific terminology. Future efforts may be warranted to further standardize terminology and definitions.

[OCULAR MANIFESTATIONS IN SYSTEMIC DISEASES].

INTRODUCTION: Uveitis and neuro-ophthalmic manifestations may indicate an underlying systemic and/or neurologic condition. A systematic approach to patients in the form of comprehensive anamnesis and thorough ocular and physical examination helps to reveal an undiagnosed condition or an evolving illness. Prompt diagnosis is of utmost importance in such cases because of potential sight-threatening and life-threatening nature of such conditions. Both subspecialties of neuro-ophthalmology and uveitis require, in many instances, a multidisciplinary approach, as emphasized in this special issue.

A novel de novo heterozygous pathogenic variant in the SDHA gene results in childhood onset bilateral optic atrophy and cognitive impairment.

Isolated defects in the mitochondrial respiratory chain complex II (CII; succinate-ubiquinone oxidoreductase) are extremely rare and mainly result from bi-allelic mutations in one of the nuclear encoded subunits: SDHA, SDHB and SDHD, which comprise CII and the assembly CII factor SDHAF1. We report an adolescent female who presented with global developmental delay, intellectual disability and childhood onset progressive bilateral optic atrophy. Whole exome sequencing of the patient and her unaffected parents identified the novel heterozygous de novo variant c.1984C > T [NM_004168.4] in the SDHA gene. Biochemical assessment of CII in the patient's derived fibroblasts and lymphocytes displayed considerably decreased CII residual activity compared with normal controls, when normalized to the integral mitochondrial enzyme citrate synthase. Protein modeling of the consequent p.Arg662Cys variant [NP-004159.2] suggested that this substitution will compromise the structural integrity of the FAD-binding protein at the C-terminus that will ultimately impair the FAD binding to SDHA, thus decreasing the entire CII activity. Our study emphasizes the role of certain heterozygous SDHA mutations in a distinct clinical phenotype dominated by optic atrophy and neurological impairment. This is the second mutation that has been reported to cause this phenotype. Furthermore, it adds developmental delay and cognitive disability to the expanding spectrum of the disorder. We propose to add SDHA to next generation sequencing gene panels of optic atrophy.

The Impact of Intra-articular Depot Betamethasone Injection on Insulin Resistance Among Diabetic Patients With Osteoarthritis of the Knee: A Case-Control Study.

OBJECTIVE: The aim of this study was to evaluate the impact of intra-articular corticosteroid injection (IACI) of depot betamethasone at the knee joint on insulin resistance (IR). METHODS: Patients with type 2 diabetes, non-insulin treated, with painful osteoarthritis of the knee were requested to participate in our study. After consent, demographic, clinical, and laboratory parameters were documented in addition to fasting blood glucose (FBG) and fasting blood insulin levels just prior to IACI of 1 mL of depot betamethasone. Fasting blood glucose and fasting blood insulin levels were repeated the next day following the IACI and 8 days later. Age- and sex-matched group of patients with type 2 diabetes from the same clinic were recruited as a control group (case-control study). Insulin resistance was calculated using Homeostasis Model Assessment-Insulin Resistance. Mann-Whitney U test, χ test, and Wilcoxon signed rank tests were used for statistical analysis. RESULTS: Eleven patients were recruited in the patients' group and 10 patients in the control group. Median FBG in the patients' group at baseline was 148 ± 51 mg/dL, and median IR was 5.12 ± 2.46. One day following the IACI, median FBG level was 247 ± 104 mg/dL (P = 0.004, compared with baseline), with median IR of 20.8 ± 7.01 (P = 0.0039). The median ratios of blood glucose and IR 1 day following the IACI compared with baseline were 1.7 and 4.1, respectively. Eight days following the IACI, mean FBG and IR levels were not significantly different from baseline. CONCLUSIONS: Intra-articular corticosteroid injection of betamethasone at the knee joint among patients with diabetes was associated with a significant increase in IR levels compared with baseline levels, 1 day following the injection. The mean percentage of increase in IR was higher than that for FBG levels.

Fornix triamcinolone injection for thyroid orbitopathy.

PURPOSE: In this pilot study we aimed to examine the association between eyelid fornices triamcinolone injections and clinical activity score in patients with active thyroid orbitopathy. METHODS: Adult patients aged 18 years or older, diagnosed with active thyroid orbitopathy and a clinical activity score ≥ 3 were recruited to this interventional prospective pilot study between 2010 and 2013. Three upper and lower fornices injections of triamcinolone acetate 20 mg (40 mg/ml) were administered at 4-week intervals. Each patient included was followed up for a period of 6 months. Clinical activity score was estimated at each monthly visit. Extraocular muscle thickness was measured by ultrasound examination at entrance and at the last visit. RESULTS: Eleven eyes of seven patients were included in our study. Initial clinical activity score was 3.81 ± 1.80 and fell to 0.63 ± 0.72 during a 6-month follow-up. There was a significant difference in clinical activity score between the baseline examination and the following visits (p-value < 0.0001). Ultrasound examination showed a significant decrease in medial and lateral rectus muscle thickness following treatment; median difference -0.93 and -0.58, respectively (p-value < 0.005). Lid retraction was reduced by the treatment. Side effects included a transitory increase in intraocular pressure in one patient, which was controlled with topical medication. CONCLUSIONS: In this pilot study a series of three separate triamcinolone fornix injections at 4-week intervals reduces the inflammatory effects of thyroid orbitopathy, as measured by clinical activity score. The treatment was simple, effective, and safe eliminating the side effects associated with systemic corticosteroid use.

[Leber's hereditary optic neuropathy].

Lebers hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by subacute severe visual loss in both eyes, which usually manifests in young adulthood. The disease has maternal inheritance due to mitochondrial DNA mutation. The final diagnosis is genetic. There is still no proven treatment, but there is significant progress in developments on the genetics of the disease to reach gene therapy. In this article we review the latest literature relevant to this disease.

A novel splice site mutation of CDHR1 in a consanguineous Israeli Christian Arab family segregating autosomal recessive cone-rod dystrophy.

PURPOSE: To investigate the genetic basis for autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. METHODS: Patients underwent a detailed ophthalmic examination, including funduscopy, electroretinography (ERG), visual field testing, and optical coherence tomography. Genome-wide homozygosity mapping using a single nucleotide polymorphism array was performed to identify homozygous regions shared between the two affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico analysis was used to predict the effect of the mutation on splicing. RESULTS: The family included two affected individuals. Clinical findings included progressive deterioration of visual acuity, photophobia, defective color vision, loss of central visual fields, pigmentary deposits localized mainly in the peripheral retina, a thinned and atrophic macular region, retinal vessel attenuation, absent ERG cone responses, and reduced ERG rod responses. Homozygosity mapping revealed several homozygous intervals shared among the affected individuals. One, a 12Mb interval on chromosome 10, included the CDHR1 gene. Direct sequencing revealed a single base transversion, c.1485+2T>G, located in the conserved donor splice site of Intron 13. This mutation cosegregated with the disease in the family, and was not detected in 208 Israeli Christian Arab control chromosomes. In silico analysis predicted that this mutation eliminates the Intron 13 donor splice site. CONCLUSIONS: Only three distinct pathogenic mutations of CDHR1 have been reported to date in patients with autosomal recessive retinal degeneration. Here we report a novel splice site mutation of CDHR1, c.1485+2T>G, underlying autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. This report expands the spectrum of pathogenic mutations of the CDHR1 gene.

Sixth Nerve Palsy in Children Etiology, Long-Term Course, and a Diagnostic Algorithm.

BACKGROUND: Acute onset strabismus is worrisome for parents and physicians. This condition is sometimes attributed to sixth cranial nerve palsy, which may be secondary to various etiologies. Debate still exists about the appropriate diagnostic approach. OBJECTIVE: The objective of this study was to describe the common etiologies of sixth nerve palsy in our pediatric population and to suggest a clear, implementable diagnostic algorithm. METHODS: The authors conducted an electronic medical review of files of patients admitted to the pediatric department at Emek Medical Center between January 2014 and April 2020. They reviewed the medical records from the study period of patients with the following diagnoses according to the International Classification of Diseases 9: sixth nerve palsy, acute infective polyneuritis, Guillain-Barré syndrome, benign intracranial hypertension, malignant neoplasm of the brain, strabismus, myasthenia gravis, and multiple sclerosis. The authors extracted information regarding clinical presentation, previous history, and diagnostic work-up, including serological testing, cerebrospinal fluid testing, and neuroimaging. Final diagnosis and clinical follow-up were assessed. RESULTS: Seventeen patients with sixth nerve palsy were identified. The most common etiologies were increased intracranial hypertension and anti-GQ1B syndrome (3 patients each). CONCLUSIONS: This is a retrospective study of patients diagnosed in one medical center. The suggested algorithm was not validated on a prospective study. The etiologies of sixth nerve palsy in children are variable. The authors suggest performing neuroimaging in all patients and considering serum and cerebrospinal fluid testing in selected patients. Initial neuroimaging combined with laboratory testing is useful and provides rational tools for proper diagnosis.

A Novel Homozygous Missense Variant in the LRRC32 Gene Is Associated With a New Syndrome of Cleft Palate, Progressive Vitreoretinopathy, Growth Retardation, and Developmental Delay.

Cleft lip and/or cleft palate are a common group of birth defects that further classify into syndromic and non-syndromic forms. The syndromic forms are usually accompanied by additional physical or cognitive abnormalities. Isolated cleft palate syndromes are less common; however, they are associated with a variety of congenital malformations and generally have an underlying genetic etiology. A single report in 2019 described a novel syndrome in three individuals, characterized by cleft palate, developmental delay and proliferative retinopathy due to a homozygous non-sense mutation in the LRRC32 gene encoding glycoprotein A repetitions predominant (GARP), a cell surface polypeptide crucial for the processing and maturation of transforming growth factor ß (TGF-ß). We describe a patient who presented with cleft palate, prenatal and postnatal severe growth retardation, global developmental delay, dysmorphic facial features and progressive vitreoretinopathy. Whole exome sequencing (WES) revealed a very rare homozygous missense variant in the LRRC32 gene, which resulted in substitution of a highly conserved isoleucine to threonine. Protein modeling suggested this variant may negatively affect GARP function on latent TGF-ß activation. In summary, our report further expands the clinical features of cleft palate, proliferative retinopathy and developmental delay syndrome and emphasizes the association of LRRC32 pathogenic variants with this new syndrome.

Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1.

PURPOSE: This study investigated the genetic basis for Usher syndrome type 1 (USH1) in four consanguineous Israeli Arab families. METHODS: Haplotype analysis for all known USH1 loci was performed in each family. In families for which haplotype analysis was inconclusive, we performed genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array. For mutation analysis, specific primers were used to PCR amplify the coding exons of the MYO7A, USH1C, and USH1G genes including intron-exon boundaries. Mutation screening was performed with direct sequencing. RESULTS: A combination of haplotype analysis and genome-wide homozygosity mapping indicated linkage to the USH1B locus in two families, USH1C in one family and USH1G in another family. Sequence analysis of the relevant genes (MYO7A, USH1C, and USH1G) led to the identification of pathogenic mutations in all families. Two of the identified mutations are novel (c.1135-1147dup in MYO7A and c.206-207insC in USH1G). CONCLUSIONS: USH1 is a genetically heterogenous condition. Of the five USH1 genes identified to date, USH1C and USH1G are the rarest contributors to USH1 etiology worldwide. It is therefore interesting that two of the four Israeli Arab families reported here have mutations in these two genes. This finding further demonstrates the unique genetic structure of the Israeli population in general, and the Israeli Arab population in particular, which due to high rates of consanguinity segregates many rare autosomal recessive genetic conditions.

Endogenous fungal endophthalmitis: risk factors, clinical course, and visual outcome in 13 patients.

AIM: To analyze the risk factors, ophthalmological features, treatment modalities and their effect on the visual outcome in patients with endogenous fungal endophthalmitis (EFE). METHODS: Data retrieved from the medical files included age at presentation to the uveitis clinic, gender, ocular symptoms and their duration before presentation, history of fever, eye affected, anatomical diagnosis and laboratory evidence of fungal infection. Medical therapy recorded included systemic antifungal therapy and its duration, use of intravitreal antifungal agents and use of oral/intravitreal steroids. Surgical procedures and the data of ophthalmologic examination at presentation and at last follow-up were also collected. RESULTS: Included were 13 patients (20 eyes, mean age 58y). Ten patients presented after gastrointestinal or urological interventions and two presented after organ transplantation. In one patient, there was no history of previous intervention. Diagnostic vitrectomy was performed in 16 eyes (80%) and vitreous cultures were positive in 10 of the vitrectomized eyes (62.5%). In only 4 patients (31%), blood cultures were positive. All patients received systemic antifungal therapy. Sixteen eyes (80%) received intravitreal antifungal agent with voriconazole being the most commonly used. Visual acuity (VA) improved from 0.9±0.9 at initial exam to 0.5±0.8 logMAR at last follow-up (P=0.03). A trend of greater visual improvement was noted in favor of eyes treated with oral steroids (±intravitreal dexamethasone) than eyes that were not treated with steroids. The most common complication was maculopathy. Twelve eyes (60%) showed no ocular complications. CONCLUSION: High index of suspicion in patients with inciting risk factors is essential because of the low yield of blood cultures and the good general condition of patients at presentation. Visual prognosis is improved with the prompt institution of systemic and intravitreal pharmacotherapy and the immediate surgical intervention. Oral±local steroids could be considered in cases of prolonged or marked inflammatory responses in order to hasten control of inflammation and limit ocular complications.

Risk of non-arteritic anterior ischaemic optic neuropathy (NAION) after cataract extraction in the fellow eye of patients with prior unilateral NAION.

AIM: To determine the risk of non-arteritic anterior ischaemic optic neuropathy (NAION) after cataract extraction (CE) in the fellow eye of patients with prior unilateral NAION. DESIGN: Retrospective, cohort study. METHODS: Medical records of patients with NAION evaluated in our institution between 1 January 1986 and 31 December 2001 were reviewed to determine the onset of NAION and the time of CE. Patients were excluded if the date of NAION and CE was unreliable, or if CE in the fellow eye was performed before the unilateral NAION. Statistical analysis was performed by including fellow eye CE as a time-dependent covariate in a Cox proportional hazards regression model of NAION incidence in the fellow eye. RESULTS: Of the 325 eligible patients, 9 (53%) of 17 patients with NAION who underwent CE in the fellow eye developed fellow eye NAION, and 59 (19%) of 308 patients with NAION who did not undergo CE in the fellow eye developed fellow eye NAION. Cataract extraction in the fellow eye increased the risk of NAION occurrence in the fellow eye by 3.6-fold (Cox regression, p=0.001). CONCLUSIONS: Patients with unilateral NAION are at a significantly higher risk of developing NAION in the fellow eye after CE.

Pre-injection of hyaluronic acid does not affect the systemic effects of intra-articular depot betamethasone injection at the knee joint.

Intra-articular injection (IAI) of both hyaluronic acid (HA) and depot-steroid preparations had the advantage of quick and prolonged favorable effects on pain relief among patients with symptomatic osteoarthritis of the knee (OAK). The effect of IAI of HA on the systemic effects of the intra-articular steroids had not been investigated. Non-selected patients attending the rheumatology clinic with symptomatic OAK who failed NSAIDS and physical therapy were offered an IAI of HA at the knee joint followed 20 min later by an IAI of 1 ml of Celestone Chronodose at the same joint (group 1). Morning serum levels of cortisol were obtained just prior to the IAI and 1, 2 and 8 days later. Demographic, clinical, and laboratory parameters were obtained also from all the patients. Age- and sex-matched group of patients from the same clinic were recruited as a control group (group 2). Mean baseline serum cortisol levels in group 1 was 381 ± 154 mmol/l vs. 376 ± 119 in group 2 (p = 0.954). Morning serum cortisol levels at day 1 and day 2 were 24 ± 6 and 22 ± 6 mmol/l, respectively, in group 1 patients vs. 27 ± 5.8 (p = 0.214) and 25 ± 5.6 mmol/l (p = 0.200), respectively, in group 2. These levels were significantly lower than baseline levels in each group. Morning serum cortisol levels at day 8 in group 1 and group 2 were 349 ± 128 and 314 ± 99 mmol/l, respectively (p = 0.419). Pre-injection of HA at the knee joint did not affect the systemic effect on the hypothalamic-pituitary-adrenal axis of IAI of Celestone Chronodose.

The effect of local injection of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis among patients with greater trochanteric pain syndrome.

Greater trochanteric pain syndrome (GTPS) is a common clinical entity for which the most effective treatment is local corticosteroid injection (LCI). There are no studies on the effect of LCI among patients with GTPS on the hypothalamic-pituitary-adrenal axis. The present study recruited nonselected patients diagnosed with GTPS. After consenting, participants received low dose (1 µg) of adrenocorticotropin hormone (ACTH) stimulation test at 09:00. Immediately following the test, participants received a LCI of 80 mg of methylprednisolone acetate at the greater trochanteric region. The ACTH stimulation test was repeated 1, 2, 4, and 6 weeks following the LCI. Cortisol samples were obtained at just prior to (basal) and 30 min (post-stimulation) following every ACTH stimulation test. Serum cortisol levels of <500 µmol/l obtained 30 min following the ACTH stimulation test were considered evidence of secondary adrenal insufficiency. The study enrolled 22 patients, 21 of whom completed participation. There were 19 female participants (~90%), and mean age of all the participants was 55.2 ± 8.6 years. Four participants showed evidence of secondary adrenal insufficiency, which was observed only at weeks 1 and 2 following the LCI. Mean serum cortisol level among these four participants 30 min following the ACTH stimulation test was 354 µmol/l, with a range of 268-430 µmol/l. LCI of 80 mg of methylprednisolone acetate in the greater trochanteric area among patients with GTPS was associated with transient secondary adrenal insufficiency in ~20% of the patients, mainly 1 week following the injection.

Heidenhain variant of Creutzfeldt-Jakob disease in a patient who had bovine bioprosthetic valve implantation.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder characterized by rapidly progressing dementia, general neurologic deterioration, and death. When the leading symptoms are visual disturbances, it is termed as the Heidenhain variant of CJD (HvCJD). CJD was reported following prion-contaminated pericardium transplants but never after bovine bioprosthetic cardiac valve. In this case report, we describe HvCJD in a patient who had a bovine bioprosthetic cardiac valve implant. An 82-year-old-woman was referred to neuro-ophthalmology clinic for unexplained visual loss that started 1 month previously. Medical history included aortic valve replacement with bovine bioprosthetic valve. On examination, best-corrected visual acuity was 20/120 in the right eye and 20/200 in the left eye; otherwise, the eye examination was normal. Humphrey visual fields revealed complete right homonymous hemianopsia. Magnetic resonance imaging (MRI) demonstrated nonspecific white matter changes. A week later, she was hospitalized due to memory impairment; repeated MRI and total body computed tomography scan showed no significant findings. Electroencephalography recordings and extremely elevated cerebrospinal fluid tau protein were compatible with CJD. The patient died 3 weeks later; autopsy was not performed. The patient had HvCJD. Ophthalmologists being first to see these patients should be aware of this diagnosis. Contaminated bovine bioprosthetic valve might be another source for prion disease. Further research is required to establish this issue.

The impact of intra-articular methylprednisolone acetate injection on fructosamine levels in diabetic patients with osteoarthritis of the knee, a case-control study.

Fructosamine is a glycated protein that reflects blood glucose control over the last 2-3 weeks. There are no studies that address the impact of intra-articular injection (IAI) of methylprednisolone acetate (MPA) on fructosamine levels among patients with type-2 diabetes and osteoarthritis of the knee (OAK). Non-selected patients attending the rheumatology or orthopedic clinic with type-2 diabetes and painful OAK, who failed non-steroidal anti-inflammatory drugs (NSAIDS) and physical therapy, were asked to participate in our study. After consent blood tests were drown for fructosamine, hemoglobin A1c (HbA1c) level, complete blood count, lipid profile, serum albumin, serum protein, c-reactive protein, and erythrocyte sedimentation rate. Demographic and different clinical parameters were also documented. Immediately after that, patients had IAI of 80 mg of MPA at the knee joint (group 1). Two to three weeks later, the same blood tests were repeated (except for HbA1c). Age- and sex-matched group of patients with type-2 diabetes and painful OAK attending the same clinics, but who were managed by NSAIDS were asked to participate as a control group (group 2) and had the same evaluation at enrollment and 2-3 weeks later, after consent. Eighteen patients from either group completed the study. Mean fructosamine level in group 1 patients was 263.7 ± 31.8 mg% prior to the IAI vs. 274.6 ± 39.3 mg% (p = 0.035), 2-3 weeks later, while mean fructosamine level in the control group (group 2) at enrollments was 274.2 ± 31.2 mg% vs. 269 ± 30.2 mg%, p = 0.509, 2-3 weeks later. There was no significant change in any other parameter tested at enrollment in either group, compared to those obtained 2-3 weeks afterwards. Body mass index was on the edge of significance as a predictor for a significant change in fructosamine level in group 1 patients. IAI of 80 mg of MPA in patients with type-2 diabetes and OAK had resulted in a significant, though mild increase in fructosamine levels 2-3 weeks later.

The association between Baker's cyst and medial meniscal tear in patients with symptomatic knee using ultrasonography.

INTRODUCTION: There are nearly no studies about the association between Baker's cyst (BC) and medial meniscal tear (MMT) using ultrasonography. PATIENTS AND METHODS: Nonselected patients who were referred for ultrasonography for the evaluation of knee pain were recruited. Demographic, clinical, and ultrasound parameters were documented. RESULTS: One-hundred and nineteen patients were included and 131 knees were evaluated. There were 59 (~50%) female patients and mean age of 46.4±17.7 years. BC was found in 31 knees (23%). BC was significantly associated with MMT (P=.029) and age (P=.002) after adjusting for other covariates. CONCLUSIONS: BC was strongly associated with MMT regardless of other intraarticular abnormalities.

The effect of intra-articular injection of Diprospan at the knee joint on the hypothalamic-pituitary-adrenal axis.

QUESTIONS UNDER STUDY: In this work we wanted to evaluate the effect of intra-articular injection (IAI) at the knee joint of 1 ml of Diprospan on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Consecutive patients attending the rheumatology or orthopaedic clinic with osteoarthritic knee pain not responding satisfactorily to medical and physical therapy were asked to participate in our study. After consent, patients had ultrasound-guided IAI of 1 ml of Diprospan, containing 2 mg of betamethasone sodium phosphate and 5 mg of betamethasone dipropionate. Demographic, clinical, laboratory and radiographic variables were documented. Just prior to the knee injection and 1, 2, 4 and 6 weeks later, patients had a 1-µg adrenocorticotropic hormone (ACTH) stimulation test. Secondary adrenal insufficiency (SAI) was defined as a poststimulation (30 minutes after ACTH injection) serum cortisol level of less than 18 µg/dl (~500 nmol/l) and lack of a rise of >6 µg/dl (~166 nmol/l) over the basal level in poststimulation serum cortisol. RESULTS: Twenty patients completed the study. There were 3 male and 17 female patients, with a mean age of 58.6±9.5 years. Six (30%) patients had evidence of SAI and in five of them it was seen at one time-point, mostly at week 2 after the IAI. In one patient, SAI was prolonged and observed from week 1 to week 4. CONCLUSIONS: IAI at the knee joint of 1 ml of Diprospan was associated with a transient high rate of SAI.