This document discusses the design and conduct of preclinical and clinical trials in ophthalmology. It describes various animal models used to study eye diseases, including monkeys, rats, mice, and their advantages and limitations. Experimental models discussed include laser-induced glaucoma, optic nerve transection, and ischemic optic neuropathy. Clinical trial inclusion and exclusion criteria are also outlined. The document emphasizes the importance of multinational collaboration for clinical trials through standardized protocols, terminology, measurement techniques, and reducing biases.
Cataract surgery is the most common surgery that we perform on a outpatient basis. Evaluation of the patient is critical and essential for a desirable visual outcome.
Cataract surgery is the most common surgery that we perform on a outpatient basis. Evaluation of the patient is critical and essential for a desirable visual outcome.
Optical Coherence Tomography in Multiple Sclerosisneurophq8
OCT is a non-invasive technology used in ophthalmology to assess retinal diseases and glaucoma. In recent years , OCT has been used to assess axonal loss and neurodegeneration in MS. This presentation will highlight the main uses of the OCT in MS and review of the literature.
Protocol for differential diagnosis of common ocular diseasesPuneet
This contains Protocol for differential diagnosis of common ocular diseases. useful for all eyecare practitioners for diagnosing Ocular conditions correctly and easily.
Evaluating the optic nerve head in glaucomaRiyad Banayot
The best method readily available to the clinician for performing this examination is high plus lens fundus biomicroscopy. Optimal magnification can be achieved by using a +60D lens which provides 1.5 times the magnification of a 90D lens. During this examination the patient's pupils must be maximally dilated with a combination of mydriatic agents such as 1% Tropicamide and 2.5% Phenylephrine.
Introduction to general ophthalmic evaluation and management principles. Lecture taken at Central Park Medical College Lahore Pakistan. The guidelines will be useful for General Practitioners as well.
Optical Coherence Tomography in Multiple Sclerosisneurophq8
OCT is a non-invasive technology used in ophthalmology to assess retinal diseases and glaucoma. In recent years , OCT has been used to assess axonal loss and neurodegeneration in MS. This presentation will highlight the main uses of the OCT in MS and review of the literature.
Protocol for differential diagnosis of common ocular diseasesPuneet
This contains Protocol for differential diagnosis of common ocular diseases. useful for all eyecare practitioners for diagnosing Ocular conditions correctly and easily.
Evaluating the optic nerve head in glaucomaRiyad Banayot
The best method readily available to the clinician for performing this examination is high plus lens fundus biomicroscopy. Optimal magnification can be achieved by using a +60D lens which provides 1.5 times the magnification of a 90D lens. During this examination the patient's pupils must be maximally dilated with a combination of mydriatic agents such as 1% Tropicamide and 2.5% Phenylephrine.
Introduction to general ophthalmic evaluation and management principles. Lecture taken at Central Park Medical College Lahore Pakistan. The guidelines will be useful for General Practitioners as well.
- An article describes what is the impact of refractive error on a layer of retina ( nerve fiber layer) in myopic subjects, Download its full text from Isra Medical Journal.
Objective: To evaluate myopic impact on thickness of nerve fiber layer of the retina in healthy myopic subjects.
Study Design: Prospective Observational study.
Place and Duration: Investigative Department of Ophthalmology of Al-Ibrahim Eye Hospital, Karachi from 1st May 2018 to 30th October 2018.
Methodology: In this study 80 eyes of myopic subjects (SE -0.5 to -11.0 DS) were enrolled. Each eye underwent through comprehensive ocular examination beginning with visual acuity, refraction, fundoscopy by slit lamp and ending up to optical coherence tomography of Nidek. Mean average peripapillary thickness of nerve fiber layer and thickness in superior, inferior, nasal and temporal quadrants was taken into consideration, calculated by Spectral Domain Optical Coherence Tomography (version 1.5.5.0).
Results: Forty subjects volunteered for study protocol among which 21 were male and 19 were female with a degree of refractive breakdown of 30% mild myopic, 50% moderately myopic and 20% highly myopic. The calculated average age was 25.0 ± 5.0 years (range 16-40 years). The average total nerve fiber layer thickness in myopic respondents was 90.85μm; superiorly 112.37μm; inferiorly 117.52μm; temporally 71.85μm and in nasal quadrant was 61.55μm. Retinal nerve fiber layer thickness was statistically significant in superior and temporal quadrant. In high myopes thickness was clinically significant in inferior quadrant in terms of quantity as compared to mild and moderate myopia
Conclusion: Average retinal nerve fiber layer thickness was significantly decreased in high myopia as compared to mild myopia while moderate group had slightly thicker thickness than high myopic group. Hence impact of dioptric power on nerve fiber layer thickness in myopic patients is significant.
A characteristic of the developing mammalian visual system is a brief interval of plasticity, termed the “critical period,” when the circuitry of
primary visual cortex is most sensitive to perturbation of visual experience. Depriving one eye of vision (monocular deprivation [MD]) during
the critical period alters ocular dominance (OD) by shifting the responsiveness of neurons in visual cortex to favor the nondeprived eye. A
disinhibitory microcircuit involving parvalbumin-expressing (PV) interneurons initiates this OD plasticity. The gene encoding the neuronal
nogo-66-receptor1(ngr1/rtn4r) is required to close the critical period.Herewecombinedmousegenetics, electrophysiology,andcircuitmapping
with laser-scanning photostimulation to investigate whether disinhibition is confined to the critical period by ngr1.We demonstrate that ngr1
mutant mice retain plasticity characteristic of the critical period as adults, and that ngr1 operates within PV interneurons to restrict the loss of
intracortical excitatory synaptic input following MD in adult mice, and this disinhibition induces a “lower PV network configuration” in both
critical-period wild-type miceandadult ngr1/mice.Wepropose that ngr1 limits disinhibition to close the critical period forODplasticityand
that a decrease in PV expression levels reports the diminished recent cumulative activity of these interneurons.
Similar to Design and Conduct of Preclinical and Clinical Trial in Opthalmology (20)
CNS Introduction, Neurons, Type of Neurons and functions, Neuroglia and types, Receptors and their types, Synapse, Neurotransmitters and their functions
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists
Design and Conduct of Preclinical and Clinical Trial in Opthalmology
1. Design and Conduct of
Preclinical and Clinical
Trials in Opthalmology
Faraza Javed
PhD Pharmacology
2. What is ophthalmology?
Opthalmos=eye
Logos=word, thought, discourse
The science of eyes is opthalmology
3. The branch of medicine concerned with
the eyes
Anatomy
Function
Disease
4. Procedures involved in clinical trials
Eye diseases are among the most
devastating disorders leading to retinal
ganglion cell (RGC) degeneration, visual field
loss and, potentially, blindness. The
pathophysiologic mechanisms underlying
optic neuropathies are not fully understood,
although research in this area is substantial.
5. Animal models are required in order to
investigate the mechanism of each disease
in detail, to improve our knowledge of how
and why optic nerve axons die, and to test
new treatment modalities. Developing an
animal model for a disease, however, is
usually complicated and challenging, and
most experimental models are remote from
the human disease.
6. There are several animal species that can be
developed as suitable models for human
disease. The advantage of using a monkey is
its close phylogeny and high homology with
humans.
Monkeys have retinal and optic nerve
anatomy that is nearly identical to human
eyes.
7. The validity of the experimental model,
however, depends upon the degree to which
it emulates the human condition, and a
primate model is considered as having the
closest compatibility for conducting research
with the goal of understanding human
diseases.
8. Indeed, testing new treatment modalities in a
monkey model is usually the last step before
embarking upon clinical trials in humans.
Unfortunately, monkeys are very expensive,
their availability is limited, and they are
difficult to handle. Experiments in monkeys
require highly experienced teams and special
housing facilities, making them beyond the
reach of many research laboratories.
9. Thus, rats and mice are commonly used to
investigate optic nerve diseases. There is
great conservation between rats, mice,
and human genomes, which allows them
to be widely used for research on human
optic nerve disease.
10. While rats are commonly used to study optic
nerve injuries, the availability of a mouse
model confers unique advantages. Genetic
studies in mice are proving to be a potent
means for learning about genes and
pathologic mechanisms that cause disease.
In addition, the genome of the mouse can be
altered by adding transgenes or altering
endogenous genes.
11. Laboratory mice live for approximately 2
years and often develop diseases that
take decades to develop in humans.
Models of optic nerve disease in the
mouse can enable us to study the
mechanism of RGC degeneration and
potential new therapies using genetic
manipulation in various transgenic and
knockout mice that are not available in
rats.
12. Experimental glaucoma in monkeys
While the most useful model for experimental
glaucoma in monkeys is produced by argon
laser photocoagulation treatment to the
trabecular meshwork. The model was first
suggested by Gaasterland and Kupfer and
later refined by Quigley and Hohman. In
order to induce elevated IOP, monkeys are
sedated and the laser beam is focused as
precisely as possible on the centre of the
mid-trabecular meshwork.
13. The recommended laser setting is a 50 m
spot diameter, 1–1.5 W, and a 0.5-s
duration. In this model, the treated eyes
develop sustained, moderately elevated IOP
with decreased outflow facility and optic
nerve cupping such as that in human
glaucoma.
14. IOP can be measured under sedation and
topical anaesthesia using the Goldman
applanation tonometer. Optic nerve
damage can be evaluated by stereoscopic
ophthalmoscopy, fundus photographs,
nerve fibre layer photographs, axonal
counting by image analysis system, and
RGC loss.
15. A second model for producing chronic
experimental glaucoma in primates was
developed by Quigley and Addicks. In this
model, extended IOP elevation was produced
by injection of autologous, fixed red blood
cells (RBC), and ghost red cells into the
anterior chamber. Filling of the anterior
chamber with blood, however, leads to the
disadvantage of poor visibility on the optic
nerve head and retina.
16. Experimental glaucoma in rats
Sustained increased IOP is
achieved by treating the
outflow channels of the
rat eye through the
peripheral cornea with a
diode laser at 532 nm
with a laser setting of
0.7 s, 0.4 W, and a spot
size of 50 m.
17. The laser beam is delivered from a slit–
lamp system without additional lenses and
with the animal under general
anaesthesia.
The rat eye is rotated manually to allow
the laser beam to be directed in a sharp
angle to the trabecular meshwork (TM).
18. Treatment takes approximately 3 min per eye
by an experienced researcher, therefore
many rats can be treated in 1 day.
19. The laser treatment is given unilaterally and
is repeated after a week if the IOP difference
between the treated eye and the fellow eye is
less than 6 mmHg. IOP is measured with the
Tonopen XL in both eyes before and
immediately after laser treatment, every 3–4
days in the first 2 weeks, and weekly
thereafter. In all, 10 measurements are
obtained for each eye from which the mean
is calculated.
20. There are three additional currently available
models for experimental glaucoma in rats, but all
of them are more time consuming and technically
more difficult to reproduce than the laser
photocoagulation model.
Morrison and co-workers increased rat IOP by
hyperosmotic saline microinjection into the
episcleral veins of Brown–Norway rats in order to
increase the outflow resistance.
21. This was sufficient for about 50% of rats to
develop elevated IOP, even though most
animals needed repeated injections. The
advantage of using Brown–Norway rats is
that IOP can be measured by a Tonopen –XL
on awake animals. General anaesthetics
were shown to have resulted in a rapid and
substantial decrease in IOP in all eyes, and
so measurements of IOP in awake animals
provide the most accurate documentation of
IOP history for rat glaucoma model studies.
22. Another rodent model for chronic glaucoma
was developed by Ueda et al. They injected
India ink into the anterior chamber 1 week
prior to laser photocoagulation treatment.
Increased IOP was achieved in all rats within
4 weeks and optic nerve damage developed
as well.
23. With recent advances in genetic
manipulation, the development of
experimental glaucoma in mice became a
matter of high priority. One of the main
obstacles was measuring IOP in the mouse
eye. Several devices were recently
developed to measure IOP in a noninvasive
way, all claiming to have the ability to
measure IOP accurately in mice.
24. Some use the Tonopen without the ocufilm
cover, while others use a modified
Goldmann tonometer, both with reliable
results.
25. Another model that has become well
established over the past few years was
developed by John et al. It consists of the
mouse strain DBA/2J that develops
glaucoma subsequent to anterior chamber
changes. The glaucoma in the DBA/2J mice
shares similarities with pigmentary
dispersion glaucoma in humans.
26. These mice develop pigment dispersion, iris
transillumination, iris atrophy, anterior
synechia, and elevated IOP. The prevalence
and severity increase with age, followed by
RGC death, and optic nerve degeneration.
Two chromosomal regions, one on
chromosome 6 and one on chromosome 4,
contribute to this glaucoma model.
27. Recently, John and his group generated and
studied mouse models with mutations in
genes that are responsible for anterior
segment dysgenesis anomalies in humans.
Developing these mouse models supports
the search for mutations in specific human
candidate genes. Although these models are
specific for unique types of glaucoma, they
can be used to test the mechanism of RGC
death in glaucoma as well as to evaluate
new treatment modalities.
28. Optic nerve transection
In rats, optic nerve transection is usually
performed using an intraorbital
approach. Using a binocular operating
microscope, the superior conjunctiva is
incised, the muscles and connective tissue
are separated, and the intraorbital optic
nerve is exposed.
29. A blade knife is used to transect the optic
nerve behind the globe, taking care not to
interfere with the blood supply and sparing
the meningeal sheaths. At the end of the
procedure, the retinas should be examined
ophthalmoscopically to assure blood vessel
patency.
30. RGCs degenerate rapidly after optic nerve
transection. One–half of them will
degenerate 4 days after optic nerve
axotomy, and it rises to about 70% in 1
week and to more than 95% in 2 weeks.
31. In monkeys, the optic nerve is transected
by a lateral approach through the skin and
the bone of the orbit approximately 6 mm
posterior to the globe. The rate of RGC
degeneration in this model is usually
slower, with about a 70% loss at 1 month
and a 90% loss at 2 months.
32. Ischaemic optic neuropathy
Recently, an animal model for anterior ischaemic
optic neuropathy (AION) in rats and mice was
developed by Bernstein et al. In this model, a
photosensitizing agent is injected intravenously
into anaesthetized rats.
33. Using a custom-designed fundus contact lens,
a laser beam directly activates the dye within
the small vessels perfusing the optic nerve
while sparing the large calibre vessels
perfusing the inner retina. Pale oedema of the
optic nerve appears shortly thereafter.
Electrophysiologically, there is a decrease in
amplitude and, histologically, there is
impairment in axonal transport. The mean
RGC loss by 39 days after the treatment is
40%. A similar model was developed for use in
mice.
35. Inclusion Criteria for Clinical Trials
1.Subjects must be capable of providing informed
consent.
2.Subjects must be able to comply with the
protocol.
3.Disease severity must be sufficient to
demonstrate a statistically significant and
clinically meaningful effect of therapy.
4.Specific diagnostic criteria must be defined to
ensure homogeneity of disease status, which can
lead to a more precise study.
5.Subjects must be capable of responding to the
proposed mechanism of action of the intervention
to be studied.
36. Exclusion Criteria for Clinical Trials
1.Subjects have concurrent disease that could
confound the response to therapy.
2.Subjects are unlikely to comply with the protocol
or likely to be lost to follow-up.
3.Subjects have known hypersensitivity or
intolerance to the proposed therapy.
4.Subjects use concomitant therapy that affects
either tear function or ocular surface integrity.
5.Subjects have had surgical or other manipulation
of the eye that could confound the outcome
parameters or interfere with the mechanism of
action of the proposed intervention to be studied.
37. FACILITATE MULTICENTER AND INTERNATIONAL
COLLABORATIVE CLINICAL TRIALS
The Subcommittee recommends the development
of criteria to be used in multinational venues.
Important aspects to consider for such international
trials are the use of uniform terminology. This may
require that terms are translated and back-
translated for clarity and accuracy It is necessary to
resolve cultural or ethnic connotations or
implications in terminology. There should be
uniform interpretation of outcome variables with
standardized protocols for measurement and
recording of data.
38. Testing procedures should be uniform, with use of
standardized reagents, standardized protocols,
and consistent recording of results. It is
necessary to maintain skill levels of data
collectors and observers, including certification of
investigators and research coordinators and
technicians. Attempts should be made to reduce
biases related to population differences (race,
ethnicity, climatic).