Determination of Sexual Dimorphism of the Human Sacrum Based on Receiver Operating Characteristic Curve Analysis of Morphometric Parameters.

Background Sex estimation of unidentified incomplete skeletons poses a challenge to paleoanthropologists and forensic experts. The sacrum is a part of the axial skeleton and contributes to the formation of the pelvic girdle. It is a significant bone for the identification of the sex in the human skeletal system due to associated functional differences of the pelvic bones in males and females. However, there is a lack of cognizance of different morphometric parameters of the sacrum which may be crucial for determining sex, particularly when a part of the bone is available. This study aimed to recognize the best morphometric parameters for the identification of the sex of the sacrum even when fragmented bones were available and compare the various parameters for sexual dimorphism in different populations. Methodology The study was conducted on 110 dry adult human sacra in the anatomy department. Out of these, 42 sacra were female and 68 were male. Morphometric measurements were performed with the help of a digital vernier caliper. Statistical analysis was performed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). Morphometric measurements of male and female sacra were compared using Student's t-test. The receiver operating characteristic (ROC) curve analysis was performed to establish the most appropriate cut-off values for each parameter. Results The mean sacral length measured from the promontory to the apex of the sacrum was higher in males compared to females (p < 0.001), whereas the sacral index was higher in female sacra in comparison to male sacra (p < 0.001). Furthermore, the mean height of the first posterior sacral foramina (PSF) was higher in male sacra bilaterally (p < 0.05). On ROC analysis, the area under the curve was 0.994 for the sacral index and 0.862 for the sacral length. Conclusions In this study, the sacral index was noted to be the most important morphometric parameter for the identification of the sex of the sacra. Additionally, the height of the S2 body, the height of the first anterior sacral foramina, and the height of the first PSF can be contemplated with an accuracy of 60-70% if only a part of the sacrum is available for determining the sex. Hence, this study emphasizes the significance of morphometric parameters of the sacrum in the determination of sex, especially in forensic cases when the skull and pelvis are fragmented or unavailable.

Xanthogranulomatous Pancreatitis -A Rare Case Defying Clinical, Radiological and Tumor Marker Diagnostics with a Review of Literature.

Xanthogranulomatous inflammation of the pancreas is an extremely rare entity mimicking pancreatic neoplasia. Elevation of tumor markers has seldom been reported in xanthogranulomatous inflammation of the pancreas, rendering the diagnosis difficult and highlighting the importance of a meticulous histopathological examination. A 58-year-old male presented with severe abdominal pain and anorexia for six months. A heterogeneously enhancing solid cystic mass was detected in the pancreatic head on contrast enhanced computed tomography. Endoscopic ultrasound guided aspiration yielded fluid showing elevated levels of CA19-9 (12000 IU/ml) and CEA (221ng/ml) with a concordant increase in the serum tumour marker levels (CA 19-9:407 IU/ml; CEA: 70 ng /ml). Clinical, radiological and biochemical evidence favouring malignancy prompted a Whipple's procedure. A thorough histopathological examination of the specimen failed to reveal malignancy. Sheets of macrophages (CD 68 +, HAM 56 +), chronic inflammatory cells, fibroblasts and proliferating capillaries replacing most of the pancreatic parenchyma were seen instead, nailing the diagnosis of xanthogranulomatous inflammation of the pancreas. To the best of our knowledge this is the first report of xanthogranulomatous inflammation of the pancreas without associated malignancy displaying an elevation of serum and fluid tumour markers. After seven months of follow up, the patient is asymptomatic and is doing well.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Multicenter Retrospective Study of 377 Adult Patients from the United States.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe mucocutaneous reaction with few large cohorts reported. This multicenter retrospective study included patients with SJS/TEN seen by inpatient consultative dermatologists at 18 academic medical centers in the United States. A total of 377 adult patients with SJS/TEN between January 1, 2000 and June 1, 2015 were entered, including 260 of 377 (69%) from 2010 onward. The most frequent cause of SJS/TEN was medication reaction in 338 of 377 (89.7%), most often to trimethoprim/sulfamethoxazole (89/338; 26.3%). Most patients were managed in an intensive care (100/368; 27.2%) or burn unit (151/368; 41.0%). Most received pharmacologic therapy (266/376; 70.7%) versus supportive care alone (110/376; 29.3%)-typically corticosteroids (113/266; 42.5%), intravenous immunoglobulin (94/266; 35.3%), or both therapies (54/266; 20.3%). Based on day 1 SCORTEN predicted mortality, approximately 78 in-hospital deaths were expected (77.7/368; 21%), but the observed mortality of 54 patients (54/368; 14.7%) was significantly lower (standardized mortality ratio = 0.70; 95% confidence interval = 0.58-0.79). Stratified by therapy received, the standardized mortality ratio was lowest among those receiving both steroids and intravenous immunoglobulin (standardized mortality ratio = 0.52; 95% confidence interval 0.21-0.79). This large cohort provides contemporary information regarding US patients with SJS/TEN. Mortality, although substantial, was significantly lower than predicted. Although the precise role of pharmacotherapy remains unclear, co-administration of corticosteroids and intravenous immunoglobulin, among other therapies, may warrant further study.

Variant Anatomy of the Hepatic Vasculature: Importance in Hepatobiliary Resections.

A variant anatomy of the hepatic vasculature has a clinically significant role in hepatobiliary transplantation, resection, tumour embolisation as well as in extrahepatic abdominal surgeries involving the stomach, pancreas or gall bladder. During routine cadaveric dissection, we observed a case of unusually small calibre hepatic artery proper. An accessory hepatic artery was seen emerging from the superior mesenteric artery to the right hepatic lobe along with an accessory hepatic vein from the right hepatic lobe that drained directly into the inferior vena cava. Such accessory hepatic vessels complicate and necessitate an alteration of surgical methodology during resection of hepatic lobes. Preoperative knowledge of variant hepatic vasculature is crucial for minimising the iatrogenic injury and facilitating successful abdominal surgeries.

Safety of non-ablative fractional laser for acne scars within 1 month after treatment with oral isotretinoin: A randomized split-face controlled trial.

BACKGROUND AND OBJECTIVE: Based on reports of poor wound healing and scarring, it is currently recommended that patients wait 6 months after completion of oral isotretinoin therapy before the safe initiation of laser treatment. Our aim was to evaluate the safety of non-ablative fractional laser (NAFL) treatment for acne scars within 1 month after isotretinoin therapy. STUDY DESIGN/METHODS: This was a randomized split-face controlled trial involving 10 patients with acne scars who had completed isotretinoin treatment. All patients received three treatments each spaced 4 weeks apart with an erbium-doped 1550 nm NAFL on one side of the face within 1 month after isotretinoin therapy. The untreated side acted as a control. Wound healing and adverse effects as well as acne scar improvement were evaluated by two blinded dermatologists. RESULTS: All patients demonstrated normal wound healing post NAFL treatments, and neither hypertrophic scars nor keloids were observed. Acne scar improvement was satisfactory. CONCLUSION: NAFL treatment for acne scarring appears to be well tolerated within 1 month of completing isotretinoin treatment. Dermatologists should reevaluate the current recommendation to wait 6 months after isotretinoin treatment for acne scar revision with lasers. Other larger studies are necessary to further challenge this dogma. Lasers Surg. Med. 49:886-890, 2017. © 2017 Wiley Periodicals, Inc.

Biometrics of Pyramidalis Muscle and its Clinical Importance.

INTRODUCTION: Pyramidalis is classified as a vestigial muscle which is frequently present. It is muscle of the anterior abdominal wall. It is thought to tense the linea alba. It has been used as a surgical landmark, source of muscle stem cells and in various surgical procedures. AIM: The aim of this study was to describe the morphometry and morphology of pyramidalis muscle in an adult Indian population and its correlation with the clinical significance. MATERIALS AND METHODS: A cadaveric study on 25 formalin fixed cadavers (males-17, females-8) was conducted in context with prevalence, morphology and morphometry of pyramidalis muscle. Statistical analysis was done using the Chi-Square test and student's t-test using SPSS version 23. RESULTS: The pyramidalis muscle was present in 92% cases, usually bilaterally (72%) than unilaterally (20%) and more frequently in males (94.11%) than in females (87.5%). This study was conducted in Department of Anatomy, Maulana Azad Medical College, New Delhi, India from August 2014 to August 2016. Bilateral asymmetry was reported. The mean length of the muscle in males and females was 52.21±14.32 and 50.13±13.62mm on the right and 53.97±15.11 and 51.22±13.78mm on the left side. No significant gender predominance existed on the right and left-sided pyramidalis lengths. The mean width of the right-sided pyramidalis in males and females was 18.35±5.15 and 17.05±4.99mm and the left-sided was 17.8±4.80 and 16.21±4.23mm without gender dimorphism. The mean thickness of the right-sided pyramidalis in males and females was 4.91±1.33 and 4.53±1.29mm and the left-sided 4.33±1.28 and 4.38±1.27mm without gender differences. The mean pyramidalis-puboumbilical index was 35.15±4.38%, 36.01±4.97% in males and females respectively. No anatomical variations with regard to origin and insertion were seen. CONCLUSION: This study provides valuable information on pyramidalis muscle which may help in appropriate understanding of anatomy, functions and clinical significance of the muscle.

A Holistic Approach to Antiaging as an Adjunct to Antiaging Procedures: A Review of the Literature.

BACKGROUND: Aging is a multifactorial process and depends on both intrinsic and extrinsic factors. Procedural options for diminishing signs of intrinsic aging and cosmetic rejuvenation have expanded dramatically. However, less attention is paid to counseling patients on options for mitigating extrinsic factors related to aging. OBJECTIVE: The objective of this study was to review changes that occur with intrinsic and extrinsic aging, and provide evidence-based holistic counseling recommendations that can be used synergistically with aesthetic procedures to maximize antiaging interventions. MATERIALS AND METHODS: A PubMed search was conducted for articles on intrinsic and extrinsic aging as it relates to skin, fat, muscle, and bone. Key clinical trials and studies on the effect of diet, hormones, exercise, sleep, stress, dental hygiene, smoking, pollution, and oxidative stress on the aging process are reviewed, and treatment recommendations are summarized based on available evidence. RESULTS: Conventional cosmetic procedures and cosmeceuticals work together with nutritious diet, exercise, dental hygiene, hormonal balance, stress reduction, smoking and pollution avoidance, and healthy sleep patterns for a better effect on antiaging. CONCLUSION: A combination approach of multiple nonsurgical modalities along with healthy lifestyle recommendations to minimize intrinsic and extrinsic aging factors allows cosmetic practitioners to target multiple facets of aging concurrently and maximize the aesthetic interventions cosmetic dermatologists/practitioners provide.

Bilateral Three-headed Biceps Brachii Muscle and its Clinical Implications.

Biceps brachii muscle frequently exhibits variant morphology in terms of origin, insertion, and mode of innervation. Nevertheless, the three-headed biceps brachii is described to be the most common variation. During routine cadaveric dissection, we came across a unique case of tricipital biceps brachii present on both the sides and variant course and branching pattern of musculocutaneous nerve. The third-headed biceps brachii emerged from the deep investing fascia of the brachialis muscle on both the sides. The musculocutaneous nerve (MCN) did not pierce the coracobrachialis muscle on the right side and terminated by supplying the muscles of the anterior compartment of the arm. However, a normal course was pursued by the MCN on the left side. Thus, scrupulous knowledge of the variant morphology of the biceps and associated structures may facilitate preoperative diagnosis and management of the upper limb diseases and circumvent iatrogenic injuries.

Complete morphometric analysis of jugular foramen and its clinical implications.

INTRODUCTION: Tumors affecting structures in the vicinity of jugular foramen such as glomus jugulare require microsurgical approach to access this region. These tumors tend to alter the normal architecture of the jugular foramen by invading it. Therefore, it is not feasible to have correct anatomic visualization of the foramen in the presence of such pathologies. Hence, a comprehensive knowledge of the jugular foramen is needed by all the neurosurgeons while doing surgery in this region. AIM: Due to the inadequate knowledge of the accurate morphology of the jugular foramen in different sexes, the aim of this osteological study was to provide a complete morphometry including gender differences and describe some morphological characteristics of the jugular foramen in an adult Indian population. MATERIALS AND METHODS: The study was done on 114 adult human dry skulls (63 males and 51 females) collected from the osteology museum in the department. Various dimensions of both endo- and exocranial aspect of jugular foramen were measured. Presence and absence of domed bony roof of jugular fossa and compartmentalization of jugular foramen were also noticed. Statistical analysis was done using Chi-square test and Student's t-test in SPSS version 23. RESULTS: All the parameters of right jugular foramen were greater than the left side, except the distance of stylomastoid foramen from lateral margin of jugular foramen (SMJF) which was greater on the left side. Gender differences between various measurements of jugular foramen, presence of dome of jugular fossa, and compartmentalization patterns were reported. CONCLUSION: This study gives knowledge about the various parameters, anatomical variations of jugular foramen in both sexes of an adult Indian population, and its clinical impact on the surgeries of this region.

Contact Urticaria to Nickel: A Series of 11 Patients Who Were Prick Test Positive and Patch Test Negative to Nickel Sulfate 2.5% and 5.0.

BACKGROUND: Nickel is the most common allergen found by patch testing; however, not all cases of nickel allergy are type 4 (delayed) allergies. Contact urticaria (CU) to nickel (immediate reaction) has been reported; however, few seem to evaluate it as per a recent published survey of American Contact Dermatitis Society members. OBJECTIVE: The aim of the study was to present a series of patients who had clinical histories suggestive of nickel allergy and yet were patch test negative but prick test positive to nickel, thus demonstrating CU. METHODS: We reviewed the charts of 11 patients who were patch test negative but prick test positive. RESULTS: All 11 patients demonstrated evidence of CU by prick testing (or closed chamber test in 1). None were patch test positive to nickel 2.5% or 5.0%. Four patients' histories mentioned reactions to various jewelry/earrings within minutes, whereas 2 histories mentioned reacting within a few hours. These histories are consistent with CU. Others (except 1 patient) recalled reacting to jewelry/earrings but did not recall a time frame. CONCLUSIONS: Our series suggests that CU to nickel may be far more common than anticipated and should be evaluated with prick testing when patients' history suggests nickel allergy and yet they are patch test negative.

Morphometric Analysis of the Occipital Condyle and Its Surgical Importance.

INTRODUCTION: The Occipital Condyle (OC) is an integral component of craniovertebral region which is predisposed to a wide array of traumatic, degenerative and neoplastic diseases. Frequent surgical interventions of OC are required for successful management of these conditions. Hence a meticulous anatomical knowledge of the OC is vital but variability in morphometric dimensions exist amongst different races and hinder the standardization of measurements. AIM: The aim of this study was to present a morphometric reference database for OC of the Indian population and enable comparisons with other populations. MATERIALS AND METHODS: The study was performed on 228 OC of 114 adult human skulls. Linear measurements of the OC were taken with the help of digital Vernier's Calliper and angular measurements were determined with software Image J. STATISTICAL ANALYSIS: Mean and standard deviation of the morphometric parameters taken into account were analysed. The comparison of morphometric dimensions of the right and left sides was carried out using Student's t-test and p-value was calculated. RESULTS: The morphometric analysis of the OC established that mean width was larger (12.97 mm) in Indians population when compared to other races. The anterior and posterior intercondylar distances as well as the distances between the tips of OC and opisthion and basion were observed to be shorter in Indians. We found a significant difference (p=0.01) among the distance between Posterior tip of Occipital Condyle (POC) and basion of the right and left sides. The sagittal condylar angle and sagittal intercondylar angle were found to be greater in our study when compared to other researchers. There existed a highly significant difference (p=0.001) between the sagittal condylar angles of the right and left sides. CONCLUSION: The present morphometric study would be valuable for the successful instrumentation of the OC as wider and ventrally oriented OC as well as smaller intercondylar distances may pose challenge to the surgeons during condylectomy. The data of present study offer anatomical reference to the surgeons and would be helpful in designing implants for the OC.

Morphometric Analysis of Sub-axial Cervical Vertebrae and Its Surgical Implications.

BACKGROUND: The predilection of the cervical spine to a wide array of traumatic, degenerative and neoplastic diseases necessitates frequent surgical interventions. For successful surgical management of these conditions, a detailed anatomical knowledge of the cervical spine is required but variability in vertebral dimensions exists amongst different races and prevents the standardization of measurements. AIM: The aim of this study was to present a morphometric reference database for cervical vertebrae of the Indian population and enable comparisons with other populations. MATERIALS AND METHODS: The study was conducted on 203 typical (C3-C6) cervical vertebrae. Linear measurements of the vertebrae were taken with the help of digital Vernier caliper and angular measurements were determined with software Image J. STATISTICAL ANALYSIS: Mean and standard deviation of the morphometric parameters taken into account were analysed. The comparison of morphometric dimensions of the right and left sides was performed using Student's t-test and p-value was calculated. RESULTS: The morphometric analysis of the cervical vertebrae demonstrated that when compared with other races, the mean height (11.39 ± 1.08 mm) and transverse diameters (22.18 ± 2.52 mm) of the vertebral body were larger but antero-posterior diameter was less, making the vertebral bodies in Indians transversely longer. The dimensions of the pedicle, laminae, articular processes and spinous process were smaller when compared to other populations. There existed a highly significant difference (p=0.002) between the widths of the right and left superior & inferior articular processes. A great disparity of the pedicle transverse angle was noted in different populations but in Indians the angle was 44.47 ± 2.81. CONCLUSION: The present morphometric study in Indian population would be valuable for the successful instrumentation of the cervical spine as smaller dimensions of the cervical vertebrae pose a challenge to the surgeons during application of plates and screws. The data would be helpful in designing spinal implants and permit identification of osteological remains.

Resident Rounds: Part III - Case Report: Argyria ­ A Case of Blue-Gray Skin.

Argyria is an uncommon blue-gray pigmentation of the skin (increased in sun-exposed areas), nail unit, and mucous membranes caused by prolonged silver exposure. Commonly occurs in the setting of occupational exposure, silver-containing medications, or systemic absorption from use of silver sulfadiazine on extensive burns/wounds. Recently, there appears to be an increase in the practice of colloidal silver ingestion given the popularity and easy availability of alternative medicines and dietary supplements containing various silver-containing compounds. We report a case of argyria in a 72-year-old male following ingestion of colloidal silver as a supplement for over 10 years. He had a diffuse, blue-gray discoloration of his face and nails. A skin biopsy was performed and histology supported the clinical diagnosis of argyria. Our objective is to increase the awareness for this rare dermatologic entity by highlighting the clinical and histological features through a case report. Dermatologists should warn patients in regards to the use of colloidal silver for alternative health practices.

Fractional carbon dioxide laser ablation for the treatment of microcystic lymphatic malformations (lymphangioma circumscriptum) in an adult patient with Klippel-Trenaunay syndrome.

BACKGROUND: Lymphangioma circumscriptum (LC) is a rare, benign, vascular malformation of dilated superficial lymphatic channels. Treatment is typically undertaken for cosmetic reasons or complications such as fluid drainage, pain, and infection risk that can negatively impact quality of life. Management of LC remains challenging because of high recurrence rates, regardless of the treatment modality chosen. OBJECTIVE: Treatment of LC with the fully-ablative carbon dioxide (CO2 ) laser has been reported widely, however, treatment with the fractionated CO2 laser has been limited to one case in the pediatric population. Our objective was to test the usefulness of the fractionated 10,600-nm CO2 laser in the management of symptomatic LC in an adult. RESULTS: We report a case of a 27-year-old female with Klippel-Trenaunay Syndrome (KTS) who presented with a 5-year history of well-circumscribed lesions on the right lateral and anterior thigh that drained clear lymphatic and serosanguineous fluid, respectively. These lesions caused her significant emotional distress because of extensive drainage. After only one treatment utilizing the fractionated 10,600-nm CO2 laser, the patient had improvement with cessation of fluid drainage, and the lesions are still asymptomatic 6 months since initial treatment. CONCLUSION: The favorable results observed in our patient suggest that fractionated CO2 laser may be an additional well-tolerated, low downtime option for palliation of symptoms in patients with LC. We recognize that short-term follow-up cannot conclusively demonstrate effectiveness and durability of this treatment and that, given the high risk of recurrence, a longer-term observation is needed before making definite conclusions. Lasers Surg. Med. 47:539-541, 2015. © 2015 Wiley Periodicals, Inc.

Perioperative Outcomes of Laparoscopic Partial Nephrectomy Stratified by Body Mass Index.

BACKGROUND AND PURPOSE: Increased body mass index (BMI) has been shown to have inferior perioperative outcomes in patients undergoing laparoscopic partial nephrectomy (LPN). The aim of this study was to determine the differences in perioperative outcomes for patients undergoing LPN in normal, overweight, and obese persons using established BMI risk categories. METHODS: A retrospective review of 488 patients undergoing LPN was performed stratifying patients according to BMI of <25 kg/m(2), 25 to 30 kg/m(2), and >30 kg/m(2). The analysis of variance test, chi-square analysis, and bivariate regression models were used to compare comorbidities and perioperative outcomes among the groups. RESULTS: One hundred and eighty nine of 369 patients were identified as being obese. Obese patients were found to have a significantly higher American Society of Anesthesiologists class (2.4 vs 2.1) than normal weight patients (P=0.03). No significant differences were demonstrated in estimated blood loss, operative time, transfusion requirement, or rate of conversion between the groups. In addition, there was no significant difference in cardiovascular, pulmonary, thromboembolic, or infectious complications between the groups. Obesity was significantly associated with bleeding necessitating angioembolization (P=0.033). CONCLUSION: LPN demonstrates equivalent perioperative outcomes in normal, overweight, and obese patients. The minimally invasive approach achieves equivalent outcomes in patients undergoing major abdominal surgery although further studies of alternate procedures are needed to validate our findings.

Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen.

Targeting antigen to dendritic cells (DCs) is a powerful and novel strategy for vaccination. Priming or loading DCs with antigen controls whether subsequent immunity will develop and hence whether effective vaccination can be achieved. The goal of our present work was to increase the potency of DC-based antitumor vaccines by overcoming inherent limitations associated with antigen stability and cross-presentation. Nanoparticles prepared from the biodegradable polymer poly(lactic-co-glycolic acid) have been extensively used in clinical settings for drug delivery and are currently the subject of intensive investigation as antigen delivery vehicles for vaccine applications. Here we describe a nanoparticulate delivery system with the ability to simultaneously carry a high density of protein-based antigen while displaying a DC targeting ligand on its surface. Utilizing a targeting motif specific for the DC-associated surface ligand DEC-205, we show that targeted nanoparticles encapsulating a MART-127-35 peptide are both internalized and cross-presented with significantly higher efficiency than isotype control-coated nanoparticles in human cells. In addition, the DEC-205-labeled nanoparticles rapidly escape from the DC endosomal compartment and do not colocalize with markers of early (EEA-1) or late endosome/lysosome (LAMP-1). This indicates that encapsulated antigens delivered by nanoparticles may have direct access to the class I cytoplasmic major histocompatibility complex loading machinery, overcoming the need for "classical" cross-presentation and facilitating heightened DC stimulation of anti-tumor CD8(+) T-cells. These results indicate that this delivery system provides a flexible and versatile methodology to deliver melanoma-associated antigen to DCs, with both high efficiency and heightened potency.

The impact of neuropathic pain in the chronic pelvic pain population.

PURPOSE: Patients with chronic pelvic pain disorders often present with neuropathic features. We examined a cohort of patients with a primary complaint of chronic pelvic pain for the presence of neuropathic pain symptoms. MATERIALS AND METHODS: Patients with chronic pelvic pain disorders from 2 tertiary referral centers were prospectively evaluated. The validated S-LANSS (Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs) survey was used to examine pain symptoms of neuropathic origin. Patients completed SF-12v2™ to assess mental/physical health domains. The 2-tailed t test and chi-square analysis were used to compare physical and mental component summaries in patients with vs without neuropathic symptoms. RESULTS: A total of 142 patients mean age of 45 years were included in analysis. Of the patients 72.5% with chronic pelvic pain carried more than 1 primary diagnosis. The S-LANSS survey identified symptoms suggestive of neuropathic pain in 44 patients (31%). A greater proportion of patients with a neuropathic component had altered sensation in the affected area (86.4% vs 24.5%). Patients with neuropathic pain scored 4.28 and 5.45 points lower on the physical and mental component summaries (p = 0.053 and 0.008, respectively). CONCLUSIONS: A large proportion of patients with chronic pelvic pain present with neuropathic features and report decreased quality of life compared with the general population. Those with neuropathic symptoms have significantly lower quality of life than those without such symptoms. Clinicians can identify patients to use targeted therapies and use a multidisciplinary approach to care.

Sustained delivery of timolol maleate from poly(lactic-co-glycolic acid)/poly(lactic acid) microspheres for over 3 months.

It is estimated that 2.2 million people have glaucoma in the US and 67 million people worldwide. The majority of cases are associated with elevated intraocular pressure (IOP) and decreasing IOP eliminates or greatly reduces degeneration in most cases, including cases in which the IOP is in the normal range but optic neuropathy occurs. Timolol maleate has the longest record of safety and efficacy to lower IOP and is administered via eye drops one or more times per day. Unfortunately, compliance is poor across patient populations leading to degeneration. Patients typically see their ophthalmologist once every 3-4 months. If one could administer a long-acting treatment while in the doctor's office, one might overcome the compliance issue and effectively preserve sight. The critical step is to develop a formulation for timolol maleate that leads to sustained delivery for greater than 90 days and would permit a different treatment paradigm, namely subconjunctival administration once every 3-4 months. By using a 50 : 50 blend of PLGA 502H and PLA, this study was able to fabricate microspheres that delivered timolol maleate continually over 107 days, well within the time frame needed to make subconjunctival administration feasible and permit a new approach to treating glaucoma and diseases of the eye more broadly.