Sildenafil in ophthalmology: An update.

Sildenafil citrate, a selective oral phosphodiesterase 5 inhibitor, is a widely used drug for erectile dysfunction that acts by elevating cGMP levels and causing smooth muscle relaxation. It also has 10% activity against PDE6, a key enzyme in phototransduction cascade in the retina. Recent ocular imaging developments have further revealed the influence of sildenafil on ocular hemodynamics, particularly choroidal perfusion. Choroidal thickness is increased, and choroidal perfusion is also enhanced by autoregulatory mechanisms that are further dependent on age and microvascular abnormalities. Studies demonstrating high intraocular pressure via a "parallel pathway" from increased choroidal volume and blood flow to the ciliary body have challenged previous concepts. Another new observation is the effect of sildenafil on bipolar cells and cyclic-nucleotide gated channels. We discuss potential deleterious effects (central serous chorioretinopathy, glaucoma, ischemic optic neuropathy, and risks to recessive carriers of retinitis pigmentosa), potential beneficial effects (ameliorate choroidal ischemia, prevent thickening of Bruch membrane, and promote recovery of the ellipsoid zone) in macular degeneration, as well as potential drug interactions of sildenafil.

Retinal toxicities of systemic anticancer drugs.

Newer anticancer drugs have revolutionized cancer treatment in the last decade, but conventional chemotherapy still occupies a central position in many cancers, with combination therapy and newer methods of delivery increasing their efficacy while minimizing toxicities. We discuss the retinal toxicities of anticancer drugs with an emphasis on the mechanism of toxicity. Uveitis is seen with the use of v-raf murine sarcoma viral oncogene homolog B editing anticancer inhibitors as well as immunotherapy. Most of the cases are mild with only anterior uveitis, but severe cases of posterior uveitis, panuveitis, and Vogt-Koyanagi-Harada-like disease may also occur. In the retina, a transient neurosensory detachment is observed in almost all patients on mitogen-activated protein kinase kinase (MEK) inhibitors. Microvasculopathy is often seen with interferon α, but vascular occlusion is a more serious toxicity caused by interferon α and MEK inhibitors. Crystalline retinopathy with or without macular edema may occur with tamoxifen; however, even asymptomatic patients may develop cavitatory spaces seen on optical coherence tomography. A unique macular edema with angiographic silence is characteristic of taxanes. Delayed dark adaptation has been observed with fenretinide. Interestingly, this drug is finding potential application in Stargardt disease and age-related macular degeneration.

1,3-Butadiene, styrene and selected outcomes among synthetic rubber polymer workers: Updated exposure-response analyses.

OBJECTIVE: - To evaluate exposure-response relationships between 1,3-butadiene and styrene and selected diseases among synthetic rubber polymer workers. METHODS: - 21,087 workers (16,579 men; 4508 women) were followed from 1943 through 2009 to determine mortality outcomes. Cox regression models estimated rate ratios (RRs) and 95% confidence intervals (CIs) by quartile of cumulative exposure to butadiene or styrene and exposure-response trends for cancers of the bladder, lung, kidney, esophagus and pancreas, and for all nonmalignant respiratory disease (NMRD), chronic obstructive pulmonary disease (COPD) and pneumonia. RESULTS: - Bladder cancer RRs were 2.13 (95% CI = 1.03 to 4.41) and 1.64 (95% CI = 0.76 to 3.54) in the highest quartiles of cumulative exposure to butadiene and styrene, respectively, and exposure-response trends were positive for both monomers (butadiene, trend p = 0.001; styrene, trend p = 0.004). Further analyses indicated that the exposure-response effect of each monomer on bladder cancer was demonstrated clearly only in the subgroup with high cumulative exposure (at or above the median) to the other monomer. Lung cancer was not associated with either monomer among men. Among women, lung cancer RRs were above 1.0 in each quartile of cumulative exposure to each monomer, but exposure-response was not seen for either monomer. Male workers had COPD RRs slightly above 1.0 in each quartile of cumulative exposure to each monomer, but there was no evidence of exposure-response among the exposed. Monomer exposure was not consistently associated with COPD in women or with the other cancer outcomes. CONCLUSIONS: - This study found a positive exposure-response relationship between monomer exposures and bladder cancer. The independent effects of butadiene and styrene on this cancer could not be delineated. In some analyses, monomer exposure was associated with lung cancer in women and with COPD in men, but inconsistent exposure-response trends and divergent results by sex do not support a causal interpretation of the isolated positive associations.

1,3-Butadiene, styrene and lymphohaematopoietic cancers among North American synthetic rubber polymer workers: exposure-response analyses.

OBJECTIVE: To evaluate exposure-response between 1,3-butadiene, styrene and lymphohaematopoietic cancers in an updated cohort of workers at six North American plants that made synthetic rubber polymers. METHODS: Employees were followed from 1943 through 2009 to determine mortality outcomes. Cox regression analyses estimated rate ratios (RRs) and 95% CIs by quartile of cumulative exposure to butadiene or styrene, measured in parts per million-years (ppm-years), and exposure-response trends for all leukaemia, lymphoid leukaemia, myeloid leukaemia, acute myeloid leukaemia, non-Hodgkin's lymphoma (NHL), multiple myeloma and all B-cell malignancies. RESULTS: Among 21 087 workers, adjusted RRs for butadiene and all leukaemia (132 deaths) rose with increasing exposure, with an RR of 2.53 (95% CI 1.37 to 4.67) in the highest exposure quartile (≥363.64 ppm-years), and the exposure-response trend was statistically significant for all leukaemia (p=0.014) and for lymphoid leukaemia (52 deaths, p=0.007). Styrene exposure-response trends for all leukaemia and lymphoid leukaemia were less consistent than those for butadiene. Cumulative exposures to butadiene and styrene were not associated consistently with myeloid leukaemias or the B-cell malignancies, NHL and multiple myeloma. CONCLUSIONS: We confirmed a positive exposure-response relationship between butadiene and all leukaemia among workers, most of whom had coexposure to styrene. Results supported an association between butadiene and lymphoid leukaemia, but not myeloid leukaemia, and provided little evidence of any association of butadiene or styrene exposures with major subtypes of B-cell malignancies other than lymphoid leukaemia, including NHL and multiple myeloma.

Paramedian transparietal approach to a dominant hemisphere intraventricular meningioma: illustrative case.

BACKGROUND: Meningiomas of the atrium of the lateral ventricle present a unique operative challenge. Parietal transcortical approaches have been described with an oblique approach, but a strictly paramedian approach may offer advantages in a dominant hemisphere atrial meningioma. OBSERVATIONS: The patient presented with several weeks of intermittent headaches. Magnetic resonance imaging (MRI) showed an enhancing intraventricular mass in the atrium of the left lateral ventricle. Three-dimensional reconstructions were created from a preoperative MRI, with 1-mm slices for neuronavigation. Diffusion tensor imaging (DTI) was obtained, and tracts were reconstructed in the patient's three-dimensional brainspace. DTI tractography delineated a paramedian transparietal corridor devoid of functional white matter tracks. The patient was positioned supine, in a semislouch position. A left parietal craniotomy was performed. Neuronavigation identified a gyrus posterior to the sensory cortex, anterior to the optic radiations and medial to superior longitudinal and arcuate fasciculus fiber tracts. The tumor was debulked to allow mobilization to coagulate capsular blood supply. Gross total resection was achieved. The patient was discharged postoperatively on day 3 without neurological deficits. LESSONS: A paramedian transparietal approach to a dominant hemisphere meningioma of the lateral ventricle can be a safe and effective way to resect tumors in this anatomically unique operative corridor.

Techniques of anterior capsulotomy in cataract surgery.

Optimal outcomes of a cataract surgery largely depend on the successful performance of an anterior capsulotomy. It is one of the most important steps of modern cataract surgery which reduces the risk of capsular tears and ensures postoperative stable intraocular lens (IOL). Anterior capsulotomy is considered ideal if it is round, continuous, well-centered, and overlaps the implanted IOL around its circumference. If any of these features is missing, it can be a cause of impedance for desired surgical and visual outcomes. Manual can opener and manual capsulorhexis are the routine standard techniques employed for manual extracapsular cataract extraction and phacoemulsification, respectively. Recent increasing use of femtosecond laser cataract surgery has allowed cataract surgeons to obviate inherent inaccuracies of manual anterior capsulotomy techniques. There is an ongoing quest to find an ideal, risk free, and surgeon-friendly technique of anterior capsulotomy that can be employed for surgery in all types of cataracts.

Comparative evaluation of femtosecond laser-assisted cataract surgery and conventional phacoemulsification in white cataract.

PURPOSE: To compare femtosecond laser-assisted capsulotomy with conventional manual capsulorhexis in cases of white cataract. PATIENTS AND METHODS: The prospective comparative study enrolled 80 eyes (80 patients) with white cataract that underwent either femtosecond laser-assisted cataract surgery (Group I, n=40) or conventional manual phacoemulsification (Group II, n=40) at a tertiary care ophthalmic institution. The groups were divided based on the patient's choice and affordability of the procedure. Capsulotomy/capsulorhexis was evaluated in terms of size, circularity index (4Π [area/perimeter2]), intraocular lens coverage, and continuity. Each group was further subdivided based on the release of white milky fluid on initiation of the capsulotomy/capsulorhexis, and the "fluid" cases were compared with the "no-fluid" cases. The primary outcome measure was capsulotomy/capsulorhexis characteristics in the two groups. The secondary outcome measures were intraoperative phacoemulsification parameters, intraoperative complications, and postoperative visual acuity. RESULTS: The size of the capsulotomy/capsulorhexis was 4.9±0.1 mm in Group I and 5.3±0.4 mm in Group II (P<0.001). Mean circularity index was 0.996±0.003 and 0.909±0.047 in Groups I and II, respectively (P<0.001). In Group I, free-floating circular capsulotomies were obtained in 52.5% (21/40) eyes; 37.5% (15/40) eyes had microadhesions; and 10% (4/40) eyes had incomplete capsulotomy in 1-2 clock hours. The incidence of residual adhesions was more in cases with release of white milky fluid (P=0.003). In Group II, a multistep capsulorhexis was performed in 70% (28/40) of the eyes. There was no difference in terms of visual outcomes and intraoperative complications. CONCLUSION: Femtosecond laser-assisted cataract surgery has the advantage of creating a circular and optimally sized capsulotomy in cases of white cataract. The release of white milky fluid during femtosecond laser delivery is the most important factor affecting the creation of a free-floating capsulotomy.

Comparative Evaluation of Retinal Nerve Fiber Layer Thickness After Conventional Brilliant Blue Assisted Internal Limiting Membrane Peeling Versus Brilliant Blue Selective Staining Using Whole Blood in Macular Hole Surgery.

BACKGROUND AND OBJECTIVE: To evaluate retinal nerve fiber layer (RNFL) thickness after conventional brilliant blue (BB) assisted macular hole (MH) surgery versus BB selective staining using whole blood (WB) in MH surgery. PATIENTS AND METHODS: Sixty eyes with stage 4 idiopathic MH with a clear media were randomly divided into two equal groups. Group A eyes underwent sequential intraoperative use of autologous heparinized WB followed by BB dye for staining internal limiting membrane, whereas eyes in group B were subjected to conventional BB staining. Clinical examination and spectral-domain optical coherence tomography was done preoperatively and postoperatively up to 6 months. RESULTS: Mean global RNFL thickness and mean temporal RNFL thickness decreased in both groups postoperatively, but the reduction in RNFL thickness in group B was greater than group A at all postoperative visits (P < .05). CONCLUSION: BB toxicity may be responsible for reduction of RNFL thickness and WB appears to protect RNFL against dye toxicity. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:436-442.].

Evaluation of a low-cost design keratoprosthesis in end-stage corneal disease: a preliminary study.

PURPOSE: To evaluate the indications, outcomes and complications of Auro keratoprosthesis (a low-cost design based on type I Boston Keratoprosthesis) in the end-stage corneal disease in a preliminary study. METHODS: In this prospective interventional study, 10 eyes of 10 patients with an end-stage corneal disease underwent implantation of Auro keratoprosthesis with the mean follow-up of 14.5±2.1 months. The indications included multiple failed grafts (n=7), aphakic bullous keratopathy (n=2) and chemical injury (n=1). The additional intraoperative procedures performed were synechiolysis (n=9), cataractous lens extraction (n=2), Ahmed glaucoma valve implantation (n=1) and vitreoretinal surgery (n=1). Antibiotic prophylaxis was administered postoperatively, and patients were followed up at 1 week, 2 weeks, 1 month and thereafter at monthly intervals. The main outcome measures were best corrected visual acuity (BCVA), retention of prosthesis, complications and need for secondary surgical interventions. RESULTS: The most common indication for keratoprosthesis implantation was graft failure (7/10, 70%). The postoperative BCVA improved to ≥20/200 in six patients. Nine out of 10 patients had retained keratoprosthesis. The complications seen were inflammatory debris behind keratoprosthesis (n=4), retroprosthetic membrane (n=2), glaucoma (n=4), small (<2 mm) sterile stromal necrosis or erosions at the graft edge (n=3) and microbial keratitis (n=1). Explantation of the keratoprosthesis was performed in one eye due to fungal keratitis. CONCLUSIONS: Auro keratoprosthesis, a low-cost keratoprosthesis, is a viable option in the end-stage corneal disease in this preliminary study. Multicentre studies with long-term follow-up are required to conclusively prove its safety and efficacy.

Bilateral recurrent ocular surface squamous cell cancer associated with epidermodysplasia verruciformis.

A 17-year-old boy, presented with a 2-year history of bilateral, recurrent ocular surface mass. Dermatological evaluation revealed the presence of multiple hypopigmented macules over his body. Skin biopsy showed features typical of epidermodysplasia verruciformis. Topical mitomycin C (0.02%) was administered in both eyes for 6 weeks (three 1-week cycles over 6 weeks). While the mass in the left eye regressed, the mass in the right eye was excised under guidance of intraoperative frozen section. Triple-freeze thaw cryotherapy of the surrounding conjunctiva along with placement of amniotic membrane graft was performed. Postoperative mitomycin C (0.02%) was administered for another 6 weeks (three 1-week cycles over 6 weeks) in both eyes. At 4 years of follow-up, no recurrence has been noted.

Peripheral ulcerative keratitis associated with chronic malabsorption syndrome and miliary tuberculosis in a child.

A 16-year-old girl presented with pain, redness, watering, and blurring of vision in her right eye. Slit lamp examination revealed the presence of peripheral ulcerative keratitis (PUK) and nodular scleritis. On clinical examination, the patient had stunted growth, low body mass index, and enlarged axillary nodes. Giardia cysts were present in the stool sample and histopathology of axillary lymph nodes showed caseating necrosis suggestive of tuberculosis (TB). A diagnosis of PUK with chronic malabsorption syndrome secondary to giardiasis and miliary TB was made. Oral metronidazole, anti-tubercular treatment, high protein diet and vitamin supplements were started. Topical steroids were started for peripheral ulcerative lesions following, which the PUK resolved.

Fulminant herpetic keratouveitis with flap necrosis following laser in situ keratomileusis: Case report and review of literature.

A 25-year-old woman presented with redness, pain, and diminution of vision that occurred 2 weeks after microkeratome-assisted laser in situ keratomileusis (LASIK). On presentation, corneal edema, Descemet membrane folds, keratic precipitates, stromal infiltrates, and flap necrosis were observed. Delayed post-LASIK microbial keratitis was diagnosed. The patient had no history of ocular herpes. Culture and scraping showed no organisms. Immunofluorescence stain was positive for the herpes simplex virus antigen. The patient was started on oral valacyclovir, and progress was monitored through serial clinical photographs and anterior segment optical coherence tomography. Resolution began within 3 days of initiating treatment and was complete in 4 weeks.

Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice.

OBJECTIVES: The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy. METHODS: In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals. KEY FINDINGS: In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group. CONCLUSIONS: The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity.

Mortality following bone metastasis and skeletal-related events among patients 65 years and above with lung cancer: A population-based analysis of U.S. Medicare beneficiaries, 1999-2006.

BACKGROUND: To quantify the impact of bone metastasis and skeletal-related events (SREs) on mortality among older patients with lung cancer. MATERIALS AND METHODS: Using the linked Surveillance, Epidemiology and End Results-Medicare database, we identified patients aged 65 years or older diagnosed with lung cancer between July 1, 1999 and December 31, 2005 and followed them to determine deaths through December 31, 2006. We classified patients as having possible bone metastasis and SREs using discharge diagnoses from inpatient claims and diagnoses paired with procedure codes from outpatient claims. We used Cox regression to estimate mortality hazards ratios (HR) among patients with bone metastasis with or without SRE, compared to patients without bone metastasis. RESULTS: Among 126,123 patients with lung cancer having a median follow-up of 0.6 years, 24,820 (19.8%) had bone metastasis either at lung cancer diagnosis (9,523, 7.6%) or during follow-up (15,297, 12.1%). SREs occurred in 12,665 (51%) patients with bone metastasis. The HR for death was 2.4 (95% CI = 2.4-2.5) both for patients with bone metastasis but no SRE and for patients with bone metastasis plus SRE, compared to patients without bone metastasis. CONCLUSIONS: Having a bone metastasis, as indicated by Medicare claims, was associated with mortality among patients with lung cancer. We found no difference in mortality between patients with bone metastasis complicated by SRE and patients with bone metastasis but without SRE.

Mortality following bone metastasis and skeletal-related events among women with breast cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999-2006.

The aim of the study is to quantify the impact of bone metastasis and skeletal-related events (SREs) on mortality in older breast cancer patients. Using the linked Surveillance, Epidemiology and End Results-Medicare database, we identified women aged 65 years or older diagnosed with breast cancer between July 1, 1999 and December 31, 2005 and followed them to determine deaths occurring through December 31, 2006. We classified patients as having possible bone metastasis and SREs using discharge diagnoses from inpatient claims and diagnoses paired with procedure codes from outpatient claims. We used Cox regression to estimate mortality hazards ratios (HR) among women with bone metastasis with or without SRE, compared with women without bone metastasis. Among 98,260 women with breast cancer (median follow-up, 3.3 years), 7,189 (7.3%) had bone metastasis either at breast cancer diagnosis (1.5%) or during follow-up (5.8%). SREs occurred in 3,319 (46%) of women with bone metastasis. HRs for risk of death were 4.9 (95% CI 4.7-5.1) and 6.2 (95% CI 5.9-6.5), respectively, for women with bone metastasis but no SRE and for women with bone metastasis plus SRE, compared with women without bone metastasis. In analyses restricted to women with bone metastasis, the adjusted HR was 1.5 (95% CI 1.4-1.6) for women with bone metastasis plus SRE, compared with women with bone metastasis but without SRE. Having a bone metastasis, as indicated by Medicare claims, was associated strongly with mortality among women with breast cancer. This association was stronger for bone metastasis complicated by SRE than for bone metastasis without SRE.

Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats.

Progesterone (a neurosteroid) is an important modulator of the nervous system functioning. Organophosphorus pesticides like phosphamidon have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was therefore designed to investigate the effects of progesterone (PROG) on phosphamidon-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the phosphamidon (1.74 mg/kg/d; p.o.) treated group at weeks 6 and 8 as compared to the control group. Two weeks treatment with PROG (15 mg/kg/d; i.p.) antagonized the effect of phosphamidon on SDL as well as TL. Phosphamidon alone produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. Treatment with PROG (15 mg/kg/d; i.p.) attenuated the effect of phosphamidon on oxidative stress. Together, the results showed that progesterone attenuated the cognitive dysfunction and increased oxidative stress induced by phosphamidon in the brain.

Effect of phosphamidon on convulsive behavior and biochemical parameters: modulation by progesterone and 4'-chlorodiazepam in rats.

Phosphamidon (PHOS) has been shown to affect nervous system adversely. The present study was designed to explore the modulation of the effects of PHOS on convulsions by neurosteroids, progesterone (PROG), and 4'-chlorodiazepam (4'-CD), in both acute and chronic seizure models. In acute study, seizures were induced by either pentylenetetrazole (PTZ) injection or maximal electroshock seizures, while in the chronic study, kindling was induced by injecting PTZ (30 mg/kg, s.c.) on alternate days three times in a week. Oxidative stress was assessed in the brain by measuring the levels of malondialdehyde (MDA), acetylcholinesterase (AChE), and non-protein thiol (NP-SH). PROG and 4'-CD were able to modulate the PHOS-induced convulsions in acute PTZ convulsions as well as in chronic kindling model. However, they failed to reverse the derangements in oxidative stress parameters of MDA and NP-SH produced by PHOS in kindled animals. PROG significantly increased the AChE activity in untreated rats, while PROG and 4'-CD reversed the AChE activity inhibition induced by PHOS. The study indicates a possible anticonvulsive mechanism of neurosteroids, since both PROG and 4'-CD reversed PHOS-induced inhibition of AChE activity. The neurosteroids seem to play a protective role in PHOS-induced convulsions besides their antioxidant property.

The delivery of evidence-based preventive care for older Americans with arthritis.

INTRODUCTION: Previous research suggests patients with rheumatoid arthritis (RA) may receive suboptimal care with respect to preventive tests and services. We evaluated the proportion of older Americans with RA, psoriatic arthritis (PsA), and osteoarthritis (OA) receiving these services and the specialty of the providers delivering this care. METHODS: Using data from 1999 to 2006 from the Medicare Chronic Conditions Warehouse, we identified persons age >/= 65 in the national 5% sample. Over the required five-year observation period, we identified tests and services recommended for older adults and the associated healthcare provider. Services of interest included dual energy x-ray absorptiometry (DXA), influenza and pneumococcal vaccination, hyperlipidemia lab testing, mammography and colonoscopy. RESULTS: After accounting for the sampling fraction, we identified 141,140 RA, 6,300 PsA, and 770,520 OA patients eligible for analysis. Over five years, a majority of RA, PsA, and OA patients were tested for hyperlipidemia (84%, 89% and 87% respectively) and received DXA (69%, 75%, and 52%). Only approximately one-third of arthritis patients received pneumococcal vaccination; 19% to 22% received influenza vaccination each year. Approximately 20% to 35% of arthritis patients never underwent mammography and colonoscopy over five years. Concomitant care from both a rheumatologist and a primary care physician was significantly associated with a greater likelihood of receiving almost all preventive tests and services. CONCLUSIONS: Among older Americans on Medicare, the absolute proportion of persons with arthritis receiving various recommended preventive services and screening tests was substantially less than 100%. Improved co-management between primary care and arthritis physicians may in part improve the delivery of preventive care for arthritis patients, but novel systematic interventions in this area are needed.