Poor responders to bevacizumab pharmacotherapy in age-related macular degeneration and in diabetic macular edema demonstrate increased risk for obstructive sleep apnea.

PURPOSE: To investigate the risk for obstructive sleep apnea (OSA) in patients with exudative age-related macular degeneration (AMD) or diabetic macular edema with poor response to anti-vascular endothelial growth factor therapy with bevacizumab (Avastin). METHODS: Age-related macular degeneration group was categorized into nonexudative, exudative, or poor response exudative. Diabetic macular edema group included patients with nonproliferative diabetic retinopathy and cystoid macular edema. Patients were categorized based on the number of intravitreal injections of bevacizumab received. Both groups were compared with age-matched controls. Patients completed a screening questionnaire to assess the risk for OSA, the main outcome measure. RESULTS: Of 103 patients with AMD, 56 (54.37%) had nonexudative AMD and 47 (45.63%) had exudative AMD, of which 14 (29.79%) had poor response exudative AMD and were at a significantly higher risk of OSA (P < 0.05). Of 30 diabetic macular edema patients with cystoid macular edema, 4 (19%) received 1 injection, 18 (81.82%) received 2 or more consecutive injections, and 16 (72.73%) received 3 or more consecutive injections. Risk for OSA increased significantly with increasing number of injections (P < 0.05). CONCLUSION: Patients with exudative AMD and diabetic macular edema with poor response to anti-vascular endothelial growth factor therapy have a significantly higher risk of OSA compared with age-matched controls and should be screened to assess the risk of OSA.

Spectral domain optical coherence tomography in the diagnosis and management of vitreoretinal interface pathologies.

The introduction of spectral domain optical coherence tomography (SD-OCT) has enhanced Vitreoretinal Interface (VRI) imaging considerably and facilitated the diagnosis, followup, prognosis determination, and management of VRI-associated pathologies. HR-OCT became a common practical tool seen in almost every ophthalmology practice. Knowledge of SD-OCT image interpretation and recognition of pathologies are required for all ophthalmologists. This paper methodically reviews the normal aging process of the VRI and discusses several commonly encountered VRI pathologies. The role of SD-OCT imaging in VRI-associated disorders such as posterior vitreous detachment, vitreomacular traction syndrome, idiopathic epiretinal membranes, lamellar holes, pseudoholes, and full thickness macular holes is portrayed. Future perspectives of new OCT technologies based on SD-OCT are discussed.

A new model of experimental autoimmune keratoconjunctivitis sicca (KCS) induced in Lewis rat by the autoantigen Klk1b22.

PURPOSE: This study was designed to generate an inducible autoimmune model of keratoconjunctivitis sicca (KCS) for study of pathogenesis of the disease. METHODS: Lewis rats were immunized with a mixture of lacrimal and salivary gland extract or recombinant mouse protein kallikrein 1b22 (Klk1b22) emulsified in complete Freund's adjuvant (CFA). For disease induction by adoptive transfer of primed cells, donor rats were received with T-cell blasts. KCS were observed by either clinical signs or histology. RESULTS: The autoantigen Klk1b22, isolated from the lacrimal and salivary glands, readily induced Sjögren's syndrome (SS)-like KCS in the recipients. The diseased animals presented the clinical and pathologic symptoms that resemble related human disease. Most immunized rats showed an increase, then a decrease in tear volume, together with corneal opacity and ocular lesions. Histologic examination revealed that the rats displayed the cardinal signs of primary SS-like KCS, including marked lymphocytic infiltration of the lacrimal and salivary glands and destruction of the acinar cells. Immunofluorescence studies showed that both CD8(+) and CD4(+) T cells were heavily infiltrated, with the former cells predominant in the damaged ducts. Finally, adoptive transfer of Klk1b22-reactive T cells induced more severe disease with earlier onset. CONCLUSIONS: Klk1b22 is an autoantigen for inducing an experimental SS-like KCS in Lewis rats. The availability of this new and reproducible rat model should provide a new and needed tool for studying the pathogenesis of SS.

CYP2D6, GST-M1 and GST-T1 enzymes: expression in parathyroid gland and association with the parathyroid hormone concentration during early renal replacement therapy.

AIMS: The purpose of this research was to characterize CYP2D6, GST-M1 and GST-T1 enzyme expression in human parathyroid tissue, and to determine whether or not there is any association between deficiencies in these enzymes and serum parathyroid hormone concentrations in patients with end-stage renal disease. METHODS: Surgical human parathyroid tissue was obtained and evaluated by immunohistochemistry for cellular localization of CYP2D6, GST-M1 and GST-T1 and colocalization of CYP2D6 with parathyroid hormone. Blood samples were collected from 328 Caucasian patients with end-stage renal disease for genetic testing of CYP2D6*3, *4, *5, *6, *7 and GST-M1*0 and GST-T1*0 alleles. Clinical chemistry data and serum intact parathyroid hormone (iPTH) concentrations were obtained from patient medical records. In 277 of the patients, the same laboratory performed all clinical tests. RESULTS: CYP2D6, GST-M1 and GST-T1 were present in human parathyroid tissue. CYP2D6 was colocalized with parathyroid hormone in parathyroid chief cells. Within the end-stage renal disease population, a nonfunctional CYP2D6 genotype was present in 18.2%[95% confidence interval (CI) 8.0, 28.4] of patients in the 1st iPTH concentration quintile (iPTH < 64 pg x mL(-1)), in 0% (95% CI 0, 7.5) of those in the 2nd quintile, in 1.8% (95% CI 0, 9.3) of those in the 3rd quintile, in 9.1% (95% CI 1.5, 16.7) of those in the 4th quintile, and in 16.7% (95% CI 6.8, 26.5) of those in the 5th quintile (iPTH > 347 pg x mL(-1)) (P = 0.001). Out of 12 CYP2D6-deficient females, seven were in the 1st iPTH concentration quintile and the remaining five were in the 5th quintile. Patients deficient in the GST-M1 and GST-T1 enzymes displayed a far more uniform frequency distribution relative to serum iPTH concentrations. CONCLUSIONS: The presence of CYP2D6, GST-M1 and GST-T1 in parathyroid cells was observed. An association is reported between a lack of CYP2D6 and iPTH concentrations in newly diagnosed end-stage renal disease patients. Gender and concomitant deficiency in GST-M1 and/or GST-T1 appear to define this association further. It remains to be established whether these associations reflect a cause-effect relationship between deficient expression of metabolizing enzymes and severity of secondary manifestation of renal failure.