A conceptual model of barriers and facilitators to primary clinical teams requesting pediatric palliative care consultation based upon a narrative review.

BACKGROUND: Despite evidence that referral to pediatric palliative care reduces suffering and improves quality of life for patients and families, many clinicians delay referral until the end of life. The purpose of this article is to provide a conceptual model for why clinical teams delay discussing palliative care with parents. DISCUSSION: Building on a prior model of parent regoaling and relevant research literature, we argue for a conceptual model of the challenges and facilitators a clinical team might face in shifting from a restorative-focused treatment plan to a plan that includes palliative aspects, resulting in a subspecialty palliative care referral. Like patients and families, clinicians and clinical teams may recognize that a seriously ill patient would benefit from palliative care and shift from a restorative mindset to a palliative approach. We call this transition "clinician regoaling". Clinicians may experience inhibitors and facilitators to this transition at both the individual and team level which influence the clinicians' willingness to consult subspecialty palliative care. The 8 inhibitors to team level regoaling include: 1) team challenges due to hierarchy, 2) avoidance of criticizing colleagues, 3) structural communication challenges, 4) group norms in favor of restorative goals, 5) diffusion of responsibility, 6) inhibited expression of sorrow, 7) lack of social support, 8) reinforcement of labeling and conflict. The 6 facilitators of team regoaling include: 1) processes to build a shared mental model, 2) mutual trust to encourage dissent, 3) anticipating conflict and team problem solving, 4) processes for reevaluation of goals, 5) sharing serious news as a team, 6) team flexibility. CONCLUSIONS: Recognizing potential team level inhibitors to transitioning to palliative care can help clinicians develop strategies for making the transition more effectively when appropriate.

Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients.

Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the "safe harbor" AAVS1 locus alleviated abnormalities in ribosome biogenesis and hematopoiesis. Our studies show that pathological features of DBA are recapitulated by iPSCs, provide a renewable source of cells to model various tissue defects, and demonstrate proof of principle for genetic correction strategies in patient stem cells.

Recent insights into inherited bone marrow failure syndromes.

PURPOSE OF REVIEW: Inherited bone marrow failure syndromes (IBMFS) are a diverse set of genetic disorders characterized by the inability of the bone marrow to produce sufficient circulating blood cells. The purpose of this review is to highlight novel findings in recent years and their impact on the understanding of IBMFS. RECENT FINDINGS: Mutations in over 80 different genes have been associated with the development of bone marrow failure (BMF). The products of the genes mutated in IBMFS frequently participate in housekeeping pathways, which are important for cell growth and division rather than being specific for hematopoiesis. The common theme of these pathways, when disturbed, is the activation of p53, leading to cell cycle arrest, senescence, and cell death. With continued improvement in therapy for IBMFS, late complications, such as development of malignancies, are seen more frequently. This highlights the importance of understanding the affected pathways and their roles in cancer development. SUMMARY: The recent advancement of our understanding of IBMFS has come largely through the identification of the genetic lesions responsible for disease and the investigations of their pathways. Applied in clinical practice, these findings make it possible to unambiguously identify mutation carriers even before the development of BMF and exclude or confirm a suspected clinical diagnosis for many of the more common IBMFS. The further characterization of the pathways leading to IBMFS is likely to reveal novel targets for screening tests, prognostic biomarkers, and improved and specific therapeutics.

Severe hyponatraemia in two patients with breast cancer caused by low-dose cyclophosphamide and precipitated by aprepitant.

Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant - a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.

Clinical implication of recent randomized control trial in primary angle-closure disease management.

Blindness due to primary angle-closure glaucoma (PACG) can be reduced significantly if the ongoing angle-closure process is arrested at an early stage. Various treatments such as laser peripheral iridotomy (LPI), iridoplasty, and clear lens extraction (CLE) have been advocated as first-line therapy for primary angle-closure (PAC), PACG, and high-risk cases of primary angle-closure suspect (PACS). EAGLE study, propagated the effectiveness of CLE over LPI for the management of primary angle closure and have sparked controversy regarding the role of LPI as a first line procedure. Randomized controlled trials (RCT), systematic reviews, and meta-analyses of RCTs done on the same question provide us with a solid base for creating guidelines/modules for our day-to-day clinical practice. A systematic review was conducted, searching several databases, including PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov, for the last 16 years (January 2005-December 2021) for RCTs with data published related to primary angle-closure disease (PACD). The search strategy included the following terms: "Primary Angle Closure disease," "Primary Angle Closure Glaucoma," "Primary Angle Closure," "Primary Angle Closure Suspect," "clear lens extraction," "laser iridotomy," "laser peripheral iridotomy," "argon laser peripheral iridoplasty," "selective laser trabeculoplasty," "trabeculectomy," "randomized control trial," and "meta-analysis of randomized control trial." In this review, we will discuss recently published RCTs (within the last 16 years) for the management of PACD and their clinical implications in day-to-day practice.

Retinal nerve fiber layer thickness in amblyopia.

Purpose: To report retinal nerve fiber layer thickness (RNFLT) in eyes with amblyopia compared with contralateral healthy eyes. Methods: In this cross-sectional study, we included patients with anisometropic amblyopia, strabismic amblyopia, and mixed amblyopia. All subjects underwent complete ophthalmic examination, including RNFLT measurement with time-domain OCT (Stratus OCT) and scanning laser polarimeter (GDX VCC). A paired "t" test was used to compare average and quadrant-wise RNFL thickness between the amblyopic and contralateral normal eyes. In addition, an analysis of variance test was used to compare various RNFL thickness parameters between the three groups. Results: A total of 33 eyes of 33 subjects with anisometropic amblyopia, 20 eyes of 20 subjects with strabismic amblyopia, and 38 eyes of 38 subjects with mixed amblyopia were included. In the anisometropic amblyopia group, the average RNFLT in the amblyopic eye was 98.2 µm and 99.8 µm in the fellow normal eye (P = 0.5), the total foveal thickness was 152.82 µm (26.78) in the anisometropic eye and 150.42 µm (23.84) in the fellow eye (P = 0.38). The difference between amblyopic and contralateral normal eye for RNFL and macular parameters was statistically insignificant in all three groups. The RNFL thickness in four quadrants was similar in the amblyopic and non-amblyopic eye between all three groups and statistically non-significant. Conclusion: Our study showed that RNFL thickness was similar in amblyopic and non-amblyopic eyes between all three amblyopia groups.

Chemical disinfectants in ophthalmic practice.

The instrumentation used in ophthalmic clinics can be a source of epidemics in health care set up. Contact tonometry with Schiotz or Applanation tonometer is associated with nosocomial epidemic keratoconjunctivitis outbreaks. Recently identified SARS-CoV-2 (COVID -19) spreads mainly via the respiratory route and fomites and can transmit through other body fluids, including tear film. Various ophthalmic instruments can become a common source of spreading cross infections. Chemical disinfection is one of the most common methods employed to decontaminate instruments and environmental surfaces and prevent transmission of infectious pathogens to patients through medical and surgical instruments. Various chemical disinfectants are available with a varied spectrum to work on a different group of organisms. In this article, we briefly cover commonly used chemical disinfectants in ophthalmic practice like Alcohol (Ethyl Alcohol, Isopropyl Alcohol), Chlorine-based solution (mainly Sodium Hypochlorite), Glutaraldehyde, Hydrogen Peroxide, Formaldehyde, Iodophors, and Quaternary Ammonium Compounds.

Optic disc morphology in primary open-angle glaucoma versus primary angle-closure glaucoma in South India.

Purpose: The aim of this study was to investigate the optic disc morphology in primary angle-closure glaucoma (PACG) versus primary open-angle glaucoma (POAG) in South Indians. Methods: A total of 60 patients (60 eyes) with PACG and 52 patients (52 eyes) with POAG were included in a cross-sectional observational study. The glaucoma diagnosis was based on a glaucomatous appearance of the optic disc correlating with visual field defects. The glaucoma was graded as early, moderate, or severe, depending upon perimetric loss. All patients underwent an ophthalmic evaluation, including visual field examination and planimetric analysis of 30° stereoscopic color optic disc photographs. Results: The POAG and PACG groups did not differ significantly in a disc or rim area, rim width, and frequencies of disc hemorrhages or rim notches. However, early POAG group (n = 15) had a significantly deeper cup depth (P = 0.01), larger beta zone (P = 0.01), and a higher frequency of localized retinal nerve fiber layer (RNFL) defects (P = 0.02) than early PACG (n = 20). Conclusion: In the early stage of the disease, POAG compared to PACG may be characterized by deeper disc cupping, a larger beta zone of peripapillary atrophy, and a higher frequency of localized RNFL defects. Such differences in early glaucoma may suggest differences in pathophysiology in POAG and PACG.

Live streaming ward rounds using wearable technology to teach medical students: a pilot study.

Background: The COVID-19 pandemic resulted in a loss of clinical clerkship opportunities for medical students. To address this problem while maintaining patient safety, this pilot study explored the feasibility of using a wearable headset to live stream teaching ward rounds to remotely based medical students. Methods: Three live streamed teaching ward rounds were delivered to three groups of medical students (n=53) using the Microsoft HoloLens 2 device and Microsoft Teams software, and results pooled for analysis. Feedback was gathered from students and instructors using the evaluation of technology-enhanced learning materials (ETELM). Patient feedback was gathered using the Communication Assessment Tool to explore any impact on interpersonal communication. Results: The response rate for the ETELM-learner perceptions was 58% (31/53), 100% for the ETELM-instructor perceptions. Students strongly agreed that the overall quality of the teaching session and instructors was excellent. However, 32% experienced issues with audio or video quality and one remote student reported cyber sickness. The statement 'educational activities encouraged engagement with session materials/content' returned the most varied response. Instructors reported technological problems with delivery while using the HoloLens 2 device and environmental noise in the ward was a disruptive factor. Preparation and skilled facilitation were key to delivering a high-quality teaching session. Patients reacted generally favourably to the technology and no negative effects on interpersonal communication were identified. Conclusion: The experience of live streamed ward rounds was well received by patients, medical students and teaching faculty. However, there remain limitations to the routine use of HoloLens 2 technology in our setting including steep learning curves, hardware costs and environmental factors such as noise and WiFi connectivity. Live streamed ward rounds have potential postpandemic implications for the judicious use of resources, and the possibility for few educationally minded clinicians to teach at scale in a patient-friendly manner.

An Interprofessional Team-Based Intervention to Address Barriers to Initiating Palliative Care in Pediatric Oncology: A Multiple-Method Evaluation of Feasibility, Acceptability, and Impact.

CONTEXT: Many children with advanced cancer are not referred to palliative care despite both professional recommendations to do so and bereaved parental preference for earlier support from sub-specialty palliative care. OBJECTIVES: To assess the feasibility, acceptability, and impact of an adaptive intervention to address individual and team-level barriers to specialty palliative care referrals. METHODS: A multiple-method approach assessed feasibility and acceptability among clinicians from pediatric oncology teams at a single institution. Quantitative measures of comfort with palliative care consultations, team cohesion, and team collaboration were conducted before and after the intervention. Number of palliative care consults were examined before, during, and after sessions. Intervention satisfaction surveys and qualitative interviews were conducted after the intervention. RESULTS: Twenty-six team members (90% of consented) attended at least one intervention session with 20 (69%) participants completing 75% or more sessions. The intervention was modified in response to participant feedback. After the intervention, participants reported greater team cohesion, comfort discussing palliative care consultation, team collaboration, process satisfaction, and decision satisfaction. Participants agreed that the training was useful, effective, helpful, and worthwhile, that they would use the skills, and that they would recommend the training to other providers. The numbers of palliative care consults increased before intervention sessions were conducted, but did not significantly change during or after the sessions. In the interviews, participants reported overall favorably regarding the intervention with some participants reporting changes in practice. CONCLUSION: An adaptive intervention to reduce barriers to initiating palliative care for pediatric oncology teams is feasible and acceptable.

Seven Types of Uncertainty When Clinicians Care for Pediatric Patients With Advanced Cancer.

CONTEXT: Clinicians deciding whether to refer a patient or family to specialty palliative care report facing high levels of uncertainty. Most research on medical uncertainty has focused on prognostic uncertainty. As part of a pediatric palliative referral intervention for oncology teams we explored how uncertainty might influence palliative care referrals. OBJECTIVES: To describe distinct meanings of the term "uncertainty" that emerged during the qualitative evaluation of the development and implementation of an intervention to help oncologists overcome barriers to palliative care referrals. METHODS: We conducted a phenomenological qualitative analysis of "uncertainty" as experienced and described by interdisciplinary pediatric oncology team members in discussions, group activities and semistructured interviews regarding the introduction of palliative care. RESULTS: We found that clinicians caring for patients with advanced cancer confront seven broad categories of uncertainty: prognostic, informational, individual, communication, relational, collegial, and inter-institutional. Each of these kinds of uncertainty can contribute to delays in referring patients to palliative care. CONCLUSION: Various types of uncertainty arise in the care of pediatric patients with advanced cancer. To manage these forms of uncertainty, providers need to develop strategies and techniques to handle professionally challenging situations, communicate bad news, manage difficult interactions with families and colleagues, and collaborate with other organizations.

Ocular manifestation in treated multibacillary Hansen's disease.

PURPOSE: To report the prevalence of ocular morbidity in patients with treated multibacillary Hansen's disease (HD) using modern ophthalmic diagnostic techniques in a rural community endemic for HD. DESIGN: Cross-sectional, observation study. PARTICIPANTS: All patients with multibacillary HD who had completed their multidrug therapy and who resided in 4 defined geographical areas in Vellore, Tamil Nadu, India. METHODS: All participants underwent a complete eye examination that included slit-lamp examination, esthesiometry, gonioscopy, applanation tonometry, and dilated fundus examination, including a stereobiomicroscopic examination of the fundus at an ophthalmic center set up for that purpose. Glaucoma suspects underwent automated perimetry using a Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA). MAIN OUTCOME MEASURES: The prevalence of various ocular disease parameters were reported as mean value with 95% confidence interval. The difference of disease prevalence between various leprosy groups was compared using an unpaired t test. The association between eye symptoms and potentially sight-threatening complications was analyzed using the chi-square test. RESULTS: Three hundred eighty-six of the 446 patients with multibacillary HD residing in the defined areas were evaluated. Four patients (1.04%; 95% confidence interval [CI], 0.0%-2.0%) were bilaterally blind; 33 (8.55%; 95% CI, 5.8%-11.3%) had unilateral blindness. Mean intraocular pressure was 12 mmHg (standard deviation, 4.1 mmHg), and prevalence of glaucoma was 3.6% (95% CI, 1.8%-5.5%). Potentially sight-threatening (PST) pathologic features (corneal anesthesia, lagophthalmos, uveitis, scleritis, and advanced glaucoma) were present in 10.4% (95% CI, 7.4%-13.4%) of patients. Significant cataracts occurred 3 times more frequently in those with polar lepromatous leprosy. The odds ratio for PST pathology in the presence of patient-reported symptoms (pain, redness, inability to close eye, burning, and irritation) was 2.9 (95% CI, 1.34-6.26). CONCLUSIONS: Patients who have completed treatment for multibacillary HD continue to have significant ocular morbidity. A history of specific eye symptoms can be the basis for referral by field staff.

Likelihood ratios: clinical application in day-to-day practice.

In this article we provide an introduction to the use of likelihood ratios in clinical ophthalmology. Likelihood ratios permit the best use of clinical test results to establish diagnoses for the individual patient. Examples and step-by-step calculations demonstrate the estimation of pretest probability, pretest odds, and calculation of posttest odds and posttest probability using likelihood ratios. The benefits and limitations of this approach are discussed.

Diagnostic capability of scanning laser polarimetry with variable cornea compensator in Indian patients with early primary open-angle glaucoma.

PURPOSE: To evaluate the diagnostic ability of scanning laser polarimetry (GDx variable corneal compensator [VCC]) for early glaucoma in Asian Indian eyes. DESIGN: Cross-sectional observational study. PARTICIPANTS: Two groups of patients (early glaucoma and normal) who satisfied the inclusion and exclusion criteria were included. Early glaucoma was diagnosed in presence of open angles, characteristic glaucomatous optic disc changes correlating with the visual field (VF) on automated perimetry (VF defect fulfilling at least 2 of 3 Anderson and Patella's criteria with mean deviation >or= -6 decibels). Normal subjects had visual acuity >or= 20/30 and intraocular pressure < 22 mmHg, with a normal optic disc and fields and no ocular abnormality. METHODS: All patients underwent complete ophthalmic evaluation, including VF examination (24-2/30-2 Swedish interactive threshold algorithm standard program) and imaging with GDx VCC. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value and negative predictive value, area under the receiving operating characteristic curve, and likelihood ratios (LRs) were calculated for various GDx VCC parameters. RESULTS: Seventy-four eyes (74 patients) with early glaucoma and 104 eyes (104 normal subjects) were enrolled. TSNIT Std Dev (temporal-superior-nasal-inferior-temporal standard deviation) had the best combination of sensitivity and specificity-61.3 and 95.2, respectively-followed by nerve fiber index score > 50 (sensitivity, 52.7%; specificity, 99%). Nerve fiber index score > 50 had positive and negative predictive values of 74.3% and 97.6%, respectively, for an assumed glaucoma prevalence of 5%. Nerve fiber index score > 50 had a positive LR (+LR) of 54.8 for early glaucoma. CONCLUSIONS: GDx VCC has moderate sensitivity, with high specificity, in the diagnosis of early glaucoma. The high +LR for the nerve fiber index score can provide valuable diagnostic information for individual patients.

Understanding and using sensitivity, specificity and predictive values.

In this article, we have discussed the basic knowledge to calculate sensitivity, specificity, positive predictive value and negative predictive value. We have discussed the advantage and limitations of these measures and have provided how we should use these measures in our day-to-day clinical practice. We also have illustrated how to calculate sensitivity and specificity while combining two tests and how to use these results for our patients in day-to-day practice.

Practical approach to medical management of glaucoma.

Primary open angle glaucoma (POAG) is usually a chronic, slowly progressive disease. At present, all resources are directed towards reduction of intraocular pressure (IOP), the only known causal and treatable risk factor for glaucoma, and medical management is frequently the first choice in most cases. With the introduction of innovative tools for early diagnosis and newer medications for treatment, decision-making in diagnosis and treatment of glaucoma has become more complex. The philosophy of glaucoma management is to preserve the visual function and quality of life (QOL) of the individual with minimum effects on QOL in terms of cost, side effects, treatment regime, follow-up schedules as well as socioeconomic burden. Our aim should be not to treat just the IOP, optic disc or visual field, but to treat the patient as a whole so as to provide maximum benefit with minimal side effects. In this article, we describe the scientific approach to medical management, mainly of POAG.

Pediatric Oncology Providers' Perceptions of a Palliative Care Service: The Influence of Emotional Esteem and Emotional Labor.

CONTEXT: Pediatric palliative care consults for children with cancer often occur late in the course of disease and close to death, when earlier involvement would reduce suffering. The perceptions that pediatric oncology providers hold about the pediatric palliative care service (PPCS) may shape referral patterns. OBJECTIVES: To explore how pediatric oncology providers at one institution perceived the hospital's PPCS and the way these perceptions may influence the timing of consultation. METHODS: We conducted semistructured qualitative interviews with pediatric oncology providers at a large children's hospital. Interviews were audio-recorded, transcribed, and analyzed by two coders using a modified grounded theory approach. RESULTS: We interviewed 16 providers (10 physicians, one nurse practitioner, two social workers, two psychologists, and one child life specialist). Three core perceptions emerged: 1) the PPCS offers a diverse range of valuable contributions to the care of children with advancing cancer; 2) providers held favorable opinions about the PPCS owing to positive interactions with individual palliative care specialists deemed extraordinarily emotionally skilled; and 3) there is considerable emotional labor involved in calling a PPCS consult that serves as a barrier to early initiation. CONCLUSION: The pediatric oncology providers in our study held a highly favorable opinion about their institution's PPCS and agreed that early consultation is ideal. However, they also described that formally consulting PPCS is extremely difficult because of what the PPCS symbolizes to families and the emotional labor that the provider must manage in introducing them. Interventions to encourage the early initiation of palliative care in this population may benefit from a focus on the emotional experiences of providers.

Diagnostic capability of optical coherence tomography (Stratus OCT 3) in early glaucoma.

PURPOSE: To evaluate the diagnostic capability of optical coherence tomography (Stratus OCT 3) for early glaucoma in Asian Indian eyes. DESIGN: Cross-sectional observational study. PARTICIPANTS: Two groups of patients (early glaucoma and normal) who satisfied the inclusion and exclusion criteria were included. Early glaucoma was diagnosed in presence of open angles, characteristic glaucomatous optic disc changes correlating with the visual field on automated perimetry (visual field defect fulfilling at least 2 of Anderson and Patella's 3 criteria with mean deviation > or = -6 dB). Normals had visual acuity > or =20/30, intraocular pressure <22 mmHg with normal optic disc and fields and no ocular abnormality. METHODS: All patients underwent complete ophthalmic evaluation including visual field examination (24-2/30-2 SITA standard program) and imaging with Stratus OCT 3. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, area under the receiving operating characteristic curve and likelihood ratios were calculated for various Stratus OCT 3 parameters. RESULTS: Seventy-two eyes (72 patients) with early glaucoma and 96 eyes (96 normal subjects) were analyzed. The inferior maximum parameter had the best combination of sensitivity and specificity, 75% (95% confidence interval [CI], 70.2-79.8%) and 89.6% (95% CI, 82.6-96.6%), respectively. The 6-o'clock parameter had a sensitivity of 61.1% (95% CI, 52.3-69.9) and specificity of 99% (95% CI, 95-100); for an assumed prevalence of 5%, the positive and negative predictive values were 75% and 98%, respectively. The positive likelihood ratio for the 6-o'clock parameter (P<5%) in early glaucoma was 61. CONCLUSIONS: Optical coherence tomography has moderate sensitivity with high specificity for the diagnosis of early glaucoma and may have a potential role in screening.

Normal age-related decay of retinal nerve fiber layer thickness.

PURPOSE: To determine the normal age-related loss of retinal nerve fiber layer thickness (RNFLT) as measured on Stratus optical coherence tomography (OCT 3; Carl Zeiss Meditec, Dublin, CA) in an Asian Indian population. DESIGN: Prospective, cross-sectional, observational study. PARTICIPANTS: One hundred eighty-seven eyes of 187 normal subjects (age range, 5-75 years) who satisfied the inclusion and exclusion criteria were included. The subjects were defined as normal if they had visual acuity of 20/30 or better, intraocular pressure less than 22 mmHg with normal optic disc, and no ocular abnormality. METHODS: All patients underwent complete ophthalmic evaluation including imaging with Stratus OCT 3. Simple linear regression was performed to study the effect of age on RNFLT, with age as the independent variable and RNFLT as the dependent variable. Spearman's correlation was studied between the age and RNFLT. An analysis of variance was applied to compare RNFLT between the different age groups. The chi-square test also was used to evaluate the relationship between age and RNFLT. MAIN OUTCOME MEASURE: Effect of age on RNFLT. RESULTS: One hundred eighty-seven eyes of 187 normal subjects were analyzed. Mean age+/-standard deviation was 33.0+/-19.7 years (range, 5-75). Average RNFLT and RNFLT by quadrant demonstrated the tendency of RNFLT to decrease with increasing age, especially after age 50 years. Average RNFLT demonstrated a negative slope of 0.16 microm/year (95% confidence interval [CI], -0.1 to -0.24). By quadrant, the superior average (negative slope, -0.23 microm/year; 95% CI, -0.1 to -0.34) showed a maximum tendency to decline with age, whereas in the inferior quadrant (negative slope, -0.08 microm/year; 95% CI, 0.05 to -0.24), the age-related decay was minimal. Six clock-hour RNFLT had a least negative slope of -0.022 microm/year (95% CI, -0.08 to -0.1). Chi-square test results showed a significant inverse relationship between age and average RNFLT (P = 0.01). CONCLUSIONS: Age-related retinal nerve fiber layer (RNFL) loss is not uniform in all the quadrants, with maximum loss in the superior quadrant, and seems to reach a maximum after the age of 50 years. Furthermore, it seems that inferior quadrant RNFL is more resistant to loss.