Novel oral medications for retinal disease: an update on clinical development.

PURPOSE OF REVIEW: Intravitreal and periocular injections for retinal disease provide a targeted delivery of medication to the eye. However, given risks of injections, including endophthalmitis, pain and treatment burden for both patients and retina specialists, there has been significant interest and effort in developing oral medications for the management of retinal disease. This article provides clinical and preclinical details of new oral medications in the pipeline for management of retinal disease. RECENT FINDINGS: Several new oral medications show clinical and preclinical promise for the management of retinal disease, including macular degeneration, diabetic retinopathy and Stargardt disease. SUMMARY: Oral medications provide promise for treating retinal disease, possibly increasing compliance, and reducing side effects of intravitreal or periocular injections. However, difficulties in this approach include systemic side effects and efficacy targeting the eye. There are multiple medications that are currently under investigation with the potential to act as stand-alone treatment or as an adjunct treatment for management of retinal diseases such as diabetic retinopathy, macular degeneration and Stargardt disease.

Efficacy and Safety of Injection Sepsivac® (Heat-killed Mycobacterium W) in Gram-negative Sepsis administered via an Intravenous Route.

BACKGROUND: As an immunomodulator, the mycobacterium w (Mw) has improved outcomes for patients suffering from severe sepsis. The traditional route of administration for Mw is intradermal (ID), which is limited to administering 0.1 mL per injection (Inj). The intravenous (IV) route can be an alternative to ID. AIMS AND OBJECTIVES: To evaluate the safety and efficacy of Inj Sepsivac® IV in gram-negative sepsis. MATERIALS AND METHODS: Present retrospective observational study was conducted in an intensive care unit (ICU) of tertiary care hospital. The study included 30 consecutive patients with presumed gram-negative sepsis within 48 hours of the first organ dysfunction. Patients received Inj Sepsivac® 0.3 mL diluted in 100 mL normal saline to be given as slow IV infusions over at least 15 minutes, every day for 3 consecutive days. Efficacy was assessed by recording the change in vital parameters, sequential organ failure assessment (SOFA) score, and laboratory investigations. Safety was evaluated by the occurrence of allergic reactions including anaphylaxis, the site of infection, and secondary infection. Each patient was followed up for 14 days from the day of enrolment. RESULTS: Mean age of patients with gram-negative sepsis was 62.67 ± 12.77 years with male preponderance (63.3%). Pneumonia (40.1%) and intraabdominal infections (26.7%) were the most common etiologies of sepsis. A significant improvement in all the vitals and mean SOFA scores was observed from day 2 onward. More than half of the patients required ventilator support [17 (56.7%)], and mortality was observed in 7 (25%) patients. None was reported to have a secondary infection. Laboratory parameters improved and oxygen requirement was reduced postday 4 till the end of treatment from baseline. CONCLUSION: The IV route of administration was found to be efficacious and safe and allow ease of administration in treating gram-negative sepsis. Further large multicentric randomized trials are required to confirm our findings.

Waste reduction through Kaizen approach: A case study of a company in India.

The growth in manufacturing activities for economic development is putting a lot of pressure on the environment. One such impact is due to generation of waste from hazardous material. The best way for hazardous waste management is either elimination or substitution with non-hazardous material. The case study in the present paper is focused on the problem of hazardous waste reduction in absence of non-hazardous substitution. In absence of any non-hazardous substitute of hazardous material, waste generation can be reduced using improvement techniques such as Kaizen to improve the manufacturing process. An Indian company improved the manufacturing procedure with very low cost to reduce waste generation of hazardous material. The outcome of this Kaizen project is the reduction of waste by 13.8% at very low cost. Along with waste reduction, cost saving, and other resource savings are another benefits. This case study provides insight about the use of Kaizen for environmentally sustainable manufacturing.

Pseudoaneurysm Arising from Mitral Aortic Intervalvular Fibrosa (P-MAIVF) Communicating with Left Atrium (LA): Multiple Detector Computed Tomography (MDCT) Evaluation.

BACKGROUND: The entity pseudoaneurysm arising from the mitral aortic intervalvular fibrosa (P-MAIVF) is a rare cardiac finding caused by multiple factors. This entity is usually diagnosed with echocardiography and confirmed with cardiac computed tomography (CT). CASE REPORT: We presented a case of congenital P-MAIVF communicating with the left atrium (LA) and an aberrant right subclavian artery, misdiagnosed as primary mitral regurgitation (MR) in transthoracic echocardiogram (TTE) due to relative contraindications to transesophageal echocardiogram (TEE), revealed in a hemophilic patient, and diagnosed with cardiac CT. CONCLUSIONS: In conclusion, cardiac CT plays a definitive role not only in anatomical assessment and confirmation of the lesion but also in primary diagnostics in patients suspected of MAIVF - especially those with relative and absolute contraindications to TEE.

Radiological illustration of spontaneous ovarian hyperstimulation syndrome.

BACKGROUND: The role of radiology is of utmost importance not only in diagnosing s-OHSS but also in ruling out other cystic ovarian diseases and to determine the underlying etiology and course of the disease. We presented a radiological algorithm for diagnosing the various causes of s-OHSS. CASE REPORT: A 26-year-old female, gravida one was referred to radiology department with history of lower abdominal pain, nausea and vomiting since 2 days which was gradual in onset and progression. The patient had no significant medical and surgical history. CONCLUSIONS: This article illustrates and emphasizes that diagnosis of s-OHSS and its etiology can be completely evaluated radiologically. Biochemical markers will confirm the radiological diagnosis.

Global reporting initiatives and firm performance: a stakeholder's perspective in Indian companies.

With the growth of the corporate sector, there is a simultaneous increase in external forces that pressurize the corporate sector to practice socially responsible behavior. Based on this, the practice of reporting sustainable and socially responsible activities is being used by companies in different manners in different countries. In view of this, the purpose of the study is to empirically analyze the financial performance of sustainability reporting and non-reporting companies from the stakeholder's perspective. The study is longitudinal, covering a time span of 22 years. The parameters of financial performance are categorized and statistically analyzed based on the stakeholders considered in the study. Based on the analysis, the study has found no evidence of difference in the financial performance from the stakeholder's perspective between sustainability reporting and non-reporting companies. The paper has contributed to the literature by analyzing the financial performance of companies from the stakeholder's perspective through longitudinal study.

Paracentral acute middle maculopathy following coronary angiography.

Purpose: To describe a case of paracentral acute middle maculopathy (PAMM) after coronary angiography. Observations: A 65-year-old female patient exhibited a dense central scotoma 5 hrs after coronary angiography. She presented the next day to the retina clinic and received a complete visual examination including slit lamp biomicroscopy, dilated fundus examination, fluorescein angiogram (FA), spectral domain optical coherence tomography (SD-OCT) and OCT-Angiography (OCT-A). She was found to have the characteristic findings of PAMM including a hyperreflective band at the inner nuclear layer (INL) with extension into the inner plexiform layer (IPL) and outer plexiform layer (OPL) on imaging. Conclusions and Importance: PAMM lesions can occur immediately following coronary angiography. The acute nature of the presentation and time to examination in this case lend further insights into the pathophysiology of PAMM. When patients undergo cardiovascular interventions and report new onset visual scotomas, the diagnosis of PAMM should be considered with referral for careful ophthalmic examination and work-up.

Syndrome of inappropriate antidiuretic hormone presenting with recurrent hiccups in a case of small cell neuroendocrine carcinoma of the lung with concomitant pulmonary tuberculosis.

Tuberculosis (TB) and lung cancer are the leading causes of mortality and morbidity in the world. The burden of TB is significantly high in developing countries causing serious public health concern, and the incidence of lung cancer is also increasing all around the world with high mortality. Pulmonary TB coexisting with lung cancer can mask the underlying disorder producing diagnostic dilemma resulting in a delay in diagnosis leading to decreased survival of the patients. Here, we report a rare case of a 66-year-old male diagnosed with microbiologically confirmed TB along with coexisting small cell neuroendocrine carcinoma of the lung presenting with syndrome of inappropriate antidiuretic hormone.

Post-traumatic cubitus varus: long-term follow-up of corrective osteotomy using the Ilizarov method of compression distraction osteogenesis.

The term cubitus varus describes the inward inclination of the supinated forearm on the extended elbow. The deformity manifests clinically as a decreased carrying angle, decreased range of motion (ROM) along with a cosmetically unsightly appearance. The aim of the present study was to evaluate the technique of compression-distraction osteogenesis using the Ilizarov apparatus in the management of patients with post-traumatic cubitus varus deformity. The objectives were to study the impact of this method on the ROM, the Humerus Elbow Wrist (HEW) angle as well as the Lateral Prominence Index. A total of 32 patients who presented with a cubitus varus deformity of ≥10° at the elbow were retrospectively analyzed using data retrieved from a computerized hospital database. All patients had undergone a mini-incision subperiosteal osteotomy followed by application of an Ilizarov frame. Cinico-radiological follow-up was carried out at regular intervals until union was achieved and yearly thereafter. The mean time to union was 11 weeks. The mean follow-up period ranged from 2 to 12 years (mean 4.0 years). Results were graded as excellent in 25 cases (78.1%), good in 2 (6.3%) and poor in 5 case (15.6%) using the grading system of Oppenheim. The mean HEW angle at final follow-up improved from 20° of varus to 6° of valgus. The mean flexion/extension improved from 121°/-3° preoperatively to 125°/-4° at final follow-up. The Mayo Elbow Performance scores at final follow-up were excellent in 23 cases, good in 7 and fair in 2. Complications encountered included superficial pintract infections in three cases, lateral condylar prominence in one case, loss of terminal flexion in three cases and valgus over-correction in one case.

Effect of multiple injections of small divided doses vs single injection of intravitreal bevacizumab on retinal neovascular model in rabbits.

BACKGROUND: To compare effects of multiple injections of small divided doses of intravitreal bevacizumab vs a single injection using a retinal neovascular model in rabbits. METHODS: We assigned 12 pigmented rabbits to four groups of three each. All groups received an intravitreal injection of vascular endothelial growth factor (VEGF, 10 microg) on the first day. Group A received an intravitreal loading dose of bevacizumab (0.5 mg) on day 3, followed by five smaller injections (0.15 mg), one every third day. Those in groups B and C received a single intravitreal injection of bevacizumab (1.25 mg) on day 3, followed by five injections of sham, one every third day in group C. Group D received only intravitreal VEGF. Follow-up examinations were performed for 26 days. RESULTS: In groups A and B, vascular changes associated with VEGF injection decreased substantially in the first 3 days, and continued to show gradual regression during each follow-up interval. No statistically significant differences were found between the changes of mean retinal thicknesses in groups A and B in both areas. In group C, the extra sham injections did not lead to any further vascular changes. The mean retinal thickness in groups B and C did not have a statistically significant difference during the follow-up period. In group D, vascular changes resolved more gradually than in other groups. The difference in retinal thickness between group D and the other groups was statistically significant on day 6 in both groups (medullary and inferior part; p = 0.0003) and in medullary wing on day 12 (p = 0.03). CONCLUSIONS: Frequent smaller doses of bevacizumab can control VEGF-induced vascular changes as well as the currently utilized model of single large monthly injections. Dividing of currently used single injection (1.25 mg) of bevacizumab to multiple small doses can control VEGF-induced vascular changes as effectively as one large injection.

Effect of artificial sweeteners on insulin resistance among type-2 diabetes mellitus patients.

INTRODUCTION: Incidence of diabetes mellitus has increased over the past few years, mainly due to our eating habits and physical inactivity. This also includes the use of artificial sweetening agents which have broadly replaced other forms of sugars and have shown a paradoxical, negative effect on blood glucose. Ingestion of these artificial sweeteners (AS) results in the release of insulin from pancreas which is mistaken for glucose (due to their sweet taste). This increases the levels of insulin in blood eventually leading to decreased receptor activity due to insulin resistance. METHODOLOGY: It is a crosssectional study that was conducted on patients diagnosed with type-2 diabetes mellitus of a tertiary care hospital in Central India. All the diabetics that presented in the OPD were divided into 2 groups based on whether they use AS (group A) or not (group B). Insulin resistance was calculated for each group using HOMA-IR and graphs were plotted. RESULTS: The HOMAIR values for Group A and B ranged from 0.9-24.33 and 0.12-10.83 with mean values 7.39 and 2.6, respectively, showing that the ones who used AS had a higher insulin resistance. The study also showed that the duration of use of artificial sweeteners had a direct impact on insulin resistance.

A passive MEMS drug delivery pump for treatment of ocular diseases.

An implantable manually-actuated drug delivery device, consisting of a refillable drug reservoir, flexible cannula, check valve, and suture tabs, was investigated as a new approach for delivering pharmaceuticals to treat chronic ocular diseases. Devices are fabricated by molding and bonding three structured layers of polydimethylsiloxane. A 30 gauge non-coring needle was used to refill the reservoir; this size maximized the number of repeated refills while minimizing damage to the reservoir. The check valve cracking pressure was 76 +/- 8.5 mmHg (mean +/- SE, n = 4); the valve sustained > 2000 mmHg of reverse pressure without leakage. Constant delivery at 1.57 +/- 0.2 microL/sec and 0.61 +/- 0.2 microL/sec (mean +/- SE, n = 4) under 500 mmHg and 250 mmHg of applied pressure, respectively, was obtained in benchtop experiments. The valve closing time constant was 10.2 s for 500 mmHg and 14.2 s for 250 mmHg. Assembled devices were successfully demonstrated in benchtop, ex vivo, and in vivo experiments.

A refillable microfabricated drug delivery device for treatment of ocular diseases.

An implantable manually-actuated microfabricated drug delivery device was demonstrated as a new approach for delivering therapeutic compounds to ocular tissue in acute in vitro, ex vivo, and in vivo studies.

Results of Ilizarov External Fixation in Rigid Equinus Deformity: An Experience of 30 Patients.

BACKGROUND: Equinus deformity is associated with congenital disorders, trauma, infections, burns and neuromuscular diseases. Tip-toe gait resulting from equinus deformity often makes ambulation difficult. Many modalities of treatment are available but most of them are challenging due to high risk of skin and soft tissue complications. The purpose of this study was to evaluate the results of Ilizarov external fixator with or without minimal soft tissue release in patients with rigid equinus deformity. MATERIALS AND METHODS: 30 patients, with 21 (70%) males and 9 (30%) females, were included in this study. 17 (56.66%) patients had right foot, 10 (33.33%) had left foot and 3 (10%) had bilateral feet involvement. 17 (56.66%) had polio, 8 (26.66%) had cerebral palsy, 3 (10%) had posttraumatic and 2 (6.66%) had post-burn equinus deformities. Mean duration of equinus deformity was 5.1 years (range 1 to 11). The ankle range of mo-tion and radiographic lateral tibiotalar angle were assessed preoperatively and at last final follow-up. Kling et al. criteria were used to assess the morphological and functional outcome. RESULTS: The mean preoperative rigid equinus deformity was -32° (range -40 to -20). The mean duration of Ilizarov external fixation required to correct the equinus deformity was 3.6 months (range 2-5.5 months). The mean preoperative tibiotalar angle was 150.2° (range 113° to 169°), which reduced to a mean angle of 102.8° (range 87° to 117°) at final follow-up. Mean dorsiflexion and plantar flexion at final follow-up was 15° (range -5° to 10°) and 31° (15° to 40°), respectively. 4 (13.33%) patients had superficial pin tract infection which was treated by serial dressings and oral antibiotics. 2 (6.66%) patients had a recurrence of 10° of equinus deformity. Excellent to good results were seen in 93.33% of patients whereas 6.66% had poor results. CONCLUSION: Ilizarov external fixation being a minimal invasive procedure allows a greater degree of equinus deformity correction.

Results of vitrectomy in Terson syndrome.

BACKGROUND: To report visual results of vitrectomy in Terson syndrome MATERIALS AND METHODS: In 11 patients, 15 eyes underwent vitreous surgery for Terson syndrome. The mean follow up was 18.3 months. RESULTS: An incomplete posterior vitreous separation was noted in 10 eyes (66.7%). An epiretinal membrane was present in 4 eyes (26.7%), and in 3 eyes, a retinal fold along the arcade was noticed. Significant visual improvement occurred in all eyes; visual acuity of 20/40 or better was achieved in 14 eyes (93.3%). Only 3 eyes developed lens opacity after surgery. CONCLUSION: Vitrectomy in Terson syndrome provides excellent visual recovery. The complication rate, including the development of cataract, is low.

Morphometric analysis of optic nerves and retina from an end-stage retinitis pigmentosa patient with an implanted active epiretinal array.

PURPOSE: To characterize optic nerve and retinal changes in a patient with end-stage retinitis pigmentosa (RP) with an implanted active epiretinal array. METHODS: A 74-year-old man with end-stage X-linked RP underwent implantation of an epiretinal array over the macula in the right eye and subsequent stimulation until his death at 5 years and 3 months after implantation. The optic nerves from this study patient, as well as those from two age-matched normal patients and two age-matched RP patients, were morphometrically analyzed against two different sets of criteria and compared. The retina underlying the array in the study patient was also morphometrically analyzed and compared with corresponding regions of the retina in the age-matched RP patients. RESULTS: Optic nerve total axon counts were significantly lower in the study patient and RP patients than in normal patients. However, there was no significant difference when comparing total axon counts from the optic nerve corresponding to the patient's implanted right eye versus the optic nerves from the RP patients (P = 0.59 and P = 0.61 using the two different criteria). Degenerated axon data quantified damage and did not show increased damage in the optic nerve quadrant that retinotopically corresponded to the site of epiretinal array implantation and stimulation. Except for the tack site, there was no significant difference when comparing the retina underlying the array and the corresponding perimacular regions of two RP patients. CONCLUSIONS: Long-term implantation and electrical stimulation with an epiretinal array did not result in damage that could be appreciated in a morphometric analysis of the optic nerve and retina.

In vivo models of proliferative vitreoretinopathy.

We outline current in vitro and in vivo models for experimental proliferative vitreoretinopathy (PVR) and provide a detailed protocol of our standardized in vivo PVR model. PVR is the leading cause of failed surgical procedures for the correction of rhegmatogenous retinal detachment. The pathogenesis of this multifactorial condition is still not completely understood. Experimental models for PVR help us understand the factors that play a role in the pathogenesis of the disease process in a controlled manner and allow for reproducible preclinical assessment of novel therapeutic interventions. We describe a cell injection model in detail that uses homologous retinal pigment epithelial (RPE) cell cultures to induce PVR over a 2-8 week period.