NO Signaling in the Cardiovascular System and Exercise.

Nitric oxide (NO) is a small molecule implicated in multiple signal transduction pathways thus contributing to the regulation of many cellular functions. The identification of NO synthase (NOS) isoforms and the subsequent characterization of the mechanisms of cell activation of the enzymes permitted the partial understanding of both the physiological and pathological processes. NO bioavailability plays an important role in the pathophysiology of cardiovascular disease and its reduction in endothelial cells is strictly associated to endothelial dysfunction which, in turn, correlates with cardiovascular mortality. Indeed, endothelial NO synthase (eNOS) has a key role in limiting cardiac dysfunction and remodeling in heart diseases, in part by decreasing myocyte hypertrophy. Conversely, exercise training is recommended to prevent and treat cardiovascular diseases-associated disorders at least by enhanced NO synthase activity and expression, and increased production of antioxidants, which prevents premature breakdown of NO. Exercise training may cause an improvement in endothelial function for both experimental animals and humans; Studies in both healthy subjects and patients with impaired NO-related vasorelaxation remarked exercise training ability to improve vascular structure and function and endothelial homeostasis. This chapter will briefly consider the importance of NO signaling in the maintenance of cardiovascular physiology, and discuss recent insights into the effect of exercise training on the signaling pathways that modulate NO synthesis and degradation in health and cardiovascular disease. In addition, we will highlight the molecular mechanisms via which microRNAs (miRs) target NO signaling in the cardiovascular system, and NO as a candidate molecule for development of new therapies.

Patient-initiated second medical opinions: their necessity and economic cost.

PURPOSE: To assess the value of patient-initiated second medical opinions (SMO). METHODS: The authors prospectively collected demographic data from 100 consecutive patients. The authors recorded major changes in the patients' care, such as inappropriate surgery recommended, inadequate treatment performed, and appropriate treatment not recommended. The authors also recorded costs incurred or saved by the patients and the third-party payers. RESULTS: In nearly 15 of the cases, the authors had major disagreements with the initial diagnosis or management. Surgery had been recommended in 28 cases. They advised against it in nine. In 72 cases, no surgery had been recommended. They advised and performed it in five. The management of five other patients was not in accordance with that recommended by large clinical trials or was inadequately done. Including the consultation fees, surgery performed or advised against, retinal angiography, and ultrasonography, the 100 SMO cost third-party payers $12,426. If the authors subtract the cost of noncontroversial surgery they recommended and if the patients had paid the consultation fee and had brought along their fluorescein angiograms, third-party payers would have saved $4,079. CONCLUSION: The savings SMO generated by eliminating unnecessary surgery resulted in improved patient care at minimal cost to third-party payers.

Macular translocation.

Macular translocation is a term used to describe any surgical procedure that involves the deliberate detachment of the retina with subsequent repositioning of the macula to a new location relative to the underlying retinal pigment epithelium. By moving the fovea away from abnormal pigment epithelium and/or choroid and repositioning it over more normal tissue, macular function can be stabilized or improved. Various techniques have been developed to accomplish this movement. Although this approach holds great promise for selected conditions (in particular, subfoveal choroidal neovascularization), the optimal technique to be used and the long-term prognosis are uncertain.

Intralenticular Candida species abscess in a premature infant.

PURPOSE: To report the clinical and histopathologic findings of a premature infant with severe retinopathy of prematurity complicated by the development of an intralenticular fungal abscess. METHODS: Case report and literature review. RESULTS: A markedly premature infant developed Candida septicemia at 29 weeks postconception. Over the ensuing 10 weeks, cataract and intraocular inflammation developed sequentially in each eye, as did progressive retinopathy of prematurity with tractional retinal detachment. Pars plana vitrectomy and lensectomy revealed intralenticular Candida species abscess. CONCLUSION: Progressive cataract and intraocular inflammation in a low birth weight infant may be caused by endogenous intraocular infection secondary to systemic candidiasis. Cataract secondary to retinopathy of prematurity is rare.

Effective macular translocation without scleral imbrication.

PURPOSE: To describe a case of effective macular translocation accomplished without scleral imbrication or extensive retinotomy. METHODS: A case report of a 59-year-old woman with subfoveal choroidal neovascularization in her left eye who underwent vitrectomy with macular detachment and fluid-air exchange. RESULTS: The macula was translocated approximately 500 microm inferiorly, allowing for photocoagulation of extrafoveal neovascularization. CONCLUSION: Limited macular translocation may be attained without scleral imbrication or significant retinotomy.

Rhegmatogenous retinal detachments with cytomegalovirus retinitis.

The most important ocular opportunistic infection in patients with AIDS is cytomegalovirus (CMV) retinitis. Management of CMV retinitis has become complex, as the life expectancy of many patients has increased exponentially. Most retinal detachments in CMV retinitis are rhegmatogenous in nature. Because of atrophic changes in the retina and alterations in the vitreous, surgical management of these detachments leads to a stepladder approach. Options include laser demarcation, scleral buckle, and vitrectomy with silicone oil. In some patients, a combination of all three procedures may be necessary. Management in all cases should be individualized, with the realization that failure of retinal reattachment may occur.

Conjunctival necrosis following the administration of subconjunctival corticosteroid.

This report describes an unusual reaction to injected subconjunctival corticosteroid. The authors examined a patient with large areas of conjunctival necrosis at the site of a previous subconjunctival corticosteroid injection. A Gram's strain and culture of the affected conjunctival area and the bottled corticosteroid suspension were negative. Necrosis of the conjunctiva is a heretofore unreported adverse reaction to a subconjunctival corticosteroid injection. These lesions probably represent a localized toxic reaction rather than a sequela of infection.

Early treatment of posterior retinopathy of prematurity: a controlled trial.

OBJECTIVE: The purpose of the study is to assess the possible benefits of early laser treatment for posterior retinopathy of prematurity (ROP) and to provide data concerning the natural history of posterior ROP. DESIGN: The study design was a prospective, multicenter, randomized trial. PARTICIPANTS: A total of 19 infants with prethreshold posterior ROP were studied. INTERVENTION: Randomization to immediate indirect laser photocoagulation or observation, with application of laser photocoagulation for those control eyes reaching threshold disease, was performed. MAIN OUTCOME MEASURES: Patients were assessed at 3 months and the anatomic outcome recorded along with any adverse treatment effects. RESULTS: An unfavorable structural outcome developed in 3 (16%) of 19 early treatment eyes compared with 3 (18%) of 17 for those treated only if threshold disease was reached. Of the 17 control eyes, 15 (88%) reached threshold disease. Progression to threshold occurred within 1 week in all but two eyes. All 12 control eyes with posterior ROP and any amount of extraretinal fibrovascular proliferation progressed to threshold disease. CONCLUSIONS: Although the number of patients studied is too small to reach statistical significance, the likelihood of a favorable outcome for eyes with prethreshold posterior ROP treated immediately with laser photocoagulation is comparable to that obtained by withholding treatment until threshold disease is reached. There is a high probability of progression from prethreshold to threshold disease, usually within 1 week or less.

Peripapillary staphyloma.

PURPOSE: To report a rare case of peripapillary staphyloma. METHOD: Case report. A 5-month-old infant was examined for esotropia associated with a retinal and optic nerve abnormality of the left eye. RESULTS: Detailed clinical examination along with diagnostic ultrasonography and electroretinography established a diagnosis of a peripapillary staphyloma of the left eye measuring 9.77 mm in depth. The patient's right eye was entirely normal, and she showed no systemic abnormalities. CONCLUSION: Although extremely rare, the peripapillary staphyloma may cause severe visual impairment of the affected eye in an otherwise healthy individual unassociated with systemic abnormalities.

Diode laser photocoagulation for retinopathy of prematurity.

OBJECTIVE: The purpose of this study was to determine the effectiveness of laser photocoagulation in eyes with threshold retinopathy of prematurity (ROP), defined as stage 3+, zone 2, with 5 or more contiguous or 8 cumulative clock hours of extraretinal fibrovascular proliferation. METHODS: Indirect ophthalmoscopic retinal examinations were performed on 18 premature infants born between 1991 and 1993 to identify those eyes with threshold ROP. Diode laser was used to treat 31 eyes within 48 hours of diagnosis. Each patient was followed post treatment at weekly intervals until regression was starting to occur. Subsequent follow-up visits were tailored to each patient. RESULTS: During the 41 to 60 month follow-up (average 49 months, median 46 months), 27 of 31 lasered eyes (87%) demonstrated regression of the extraretinal neovascularization, and 26 (84%) had functional vision. This includes two Stage 4B eyes that were reattached with scleral buckles. Twenty-two eyes (71%) were myopic and four (13%) progressed to stage 5 retinal detachment that could not be repaired. No cataracts occurred in this group of patients. CONCLUSIONS: Although a potentially blinding disorder, threshold ROP is, in many cases, treatable with laser photocoagulation, which may be easier to administer than cryotherapy. Follow-up of patients treated with diode laser demonstrates that functional vision is attainable.

Use of perflubron as a new temporary vitreous substitute and manipulation agent for vitreoretinal surgery. Wills Eye Hospital Perflubron Study Group.

PURPOSE: The authors determine the intraocular tolerance of a new widely used liquid perfluorocarbon, perfluoroctylbromide (perflubron). METHODS: Pars plana vitrectomy was performed on 54 eyes of 54 patients with vitreoretinal disorders at three centers. Diagnoses included giant retinal tears, proliferative vitreoretinopathy, and dislocated intraocular and crystalline lenses. At the conclusion of the vitrectomy, perflubron was removed. RESULTS: Perflubron was efficacious for vitreoretinal manipulation. Of the 45 eyes with retinal detachment, 23 (51.1%) of the retinas were reattached after a single surgery; redetachment occurred in 22 (48.9%) after the initial procedure, and further surgery was necessary to reattach the retina. Final retinal reattachment was achieved in 40 (88.9%) eyes. Mean visual acuity improvement was six lines (P < 0.0019). Visualization of the water/perfluorocarbon interface was good. There was no evidence of adverse effects from perflubron on the retina, lens, or anterior segment. CONCLUSION: Findings indicate that perflubron is safe for temporary intraoperative use intravitreally. The absence of adverse effects is consistent with the properties of perflubron that our group has studied in the eyes of animals and in other uses in human patients.

Retinopathy of prematurity: diagnosis and management [continuing education credit].

1. Despite advancements in neonatal and ophthalmic care, over 500 infants per year are blinded by retinopathy of prematurity (ROP). 2. Cryotherapy and laser photocoagulation have greatly improved the prognosis for infants with ROP. 3. Despite timely intervention, some infants with ROP will develop retinal detachment.

Extracapsular cataract extraction with placement of a posterior chamber lens in patients with diabetic retinopathy.

PURPOSE: The authors evaluated factors that might influence the outcome of extracapsular cataract extraction with placement of a posterior chamber lens in patients with diabetic retinopathy. The factors included patient age and sex, severity of the retinopathy, preoperative laser photocoagulation, vitrectomy, and posterior capsulotomy. METHODS: The records of 109 patients who had been examined by the authors before cataract surgery were retrospectively reviewed. RESULTS: The final visual acuity in only 48% of the eyes was 20/40 or better, and 28% had 20/200 or worse visual acuity. Only 65% had an improvement in visual acuity of two or more Snellen lines. Eyes with preoperative macular edema had a poorer visual outcome than eyes without. Macular edema and ischemia accounted for 70% of the eyes with a final visual acuity of 20/50 or worse. The authors found that age was a strong predictor of final visual acuity and chances of improvement. In patients 63 years of age and younger, 58% had 20/40 or better and 81% had improved visual acuity. In patients 64 years of age and older, only 38% had 20/40 or better and only 54% were improved. Supplementary panretinal photocoagulation was required in 37% of patients who had received it preoperatively. Neovascularization of the iris developed in 6% of patients. Posterior capsulotomy did not cause an increased incidence of neovascularization of the iris or in the development or progression of proliferative retinopathy or macular edema. CONCLUSION: The prognosis of patients with diabetic retinopathy about to undergo cataract surgery, even extracapsular cataract extraction with placement of a posterior chamber lens, is guarded.

A simple technique for controlled subretinal injections.

Recently developed vitrectomy techniques for management of choroidal neovascular membranes and subretinal hemorrhages often involve the subretinal injection of fluid materials. A simple, inexpensive infusion system that allows for the controlled injection of fluid, allowing use of a minimal amount of fluid and maximizing surgeon control, is described.