This document summarizes several studies and clinical trials related to the treatment of diabetic retinopathy and diabetic macular edema. It discusses the Diabetic Retinopathy Study (DRS) and Early Treatment Diabetic Retinopathy Study (ETDRS) which established laser photocoagulation as the standard treatment for proliferative diabetic retinopathy and diabetic macular edema. It also summarizes the Diabetic Retinopathy Clinical Research Network (DRCR.Net) which conducted several clinical trials comparing treatments for diabetic macular edema such as anti-VEGF injections and laser photocoagulation. The document provides high-level overviews of many landmark studies that helped advance the treatment of diabetic eye disease.
Most retinal surgeons are trained to create formal retinal drawings of the fundus.
Retinal drawings are useful to document pathology, although more and more people now prefer fundus photographs.
Can be used for serial follow up of patients to document changes in the pathology.
Most retinal surgeons are trained to create formal retinal drawings of the fundus.
Retinal drawings are useful to document pathology, although more and more people now prefer fundus photographs.
Can be used for serial follow up of patients to document changes in the pathology.
updating in diabetic macular edema including old and new approach era, including DRCR protocol
how to approach, how to treat, when to surgery
plus knownledge about anti-VEGF therapy up to date
Aim: To compare one Field Of View (1 - FOV) and two Field Of View (2 - FOV) photography for diabetic retinopathy detection by assessing and comparing disease level and outcome.
Methods: A retrospective audit of a random sample of 500 patients with known proliferative diabetic retinopathy (PDR or R3), and 500 non-proliferative diabetic retinopathy (NPDR or R2). Images were re-assessed according to the English program criteria for DR levels using 1-FOV.
Novel Development in treatment of Diabetic Macular Edema, by Dr. Fritz Allen, presented at VO, Lecture Series 11, Feb 20, 2011
COPE Course ID: 30657-PS
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
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Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
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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.
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
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3. DRS – INTRODUCTION (1)
• laser photocoagulation – introduced in 1959
• Inadequate evidence of actual value of laser photocoagulation
• DRS started in 1971
4. DRS (2) - PURPOSE
• To determine whether laser photocoagulation helps to prevent
severe visual loss from PDR
• To determine whether a difference exists in the efficacy and safety of
argon versus xenon photocoagulation for PDR
5. DRS – STUDY PATTERN (3)
• Eligibility criteria – presence of
PDR
Each Patient’s
eyes –
randomized
Immediate
Photocoagulation
Scatter – Panretinal
Local – direct confluent treatment
of new vessels
Focal – for macular edema
Follow up without
treatment
Randomized
Argon Xenon
6. DRS – RESULTS (4)
• Photocoagulation (both argon & xenon) reduced risk of visual loss by
50 % or more compared with no treatment
• Study identified a stage of retinopathy – High Risk PDR, where
benefits of photocoagulation definitely outweighed risks
• Severe vision loss (5 year rate) reduced from 50% without treatment
to 20% with treatment
• No benefit for eyes with severe NPDR/ PDR without HRC
7. DRS – CONCLUSION (5)
• Both argon & xenon laser photocoagulation inhibited progression of
retinopathy
• PDR with HRC – prompt treatment with PRP
• Less severe retinopathy – findings do not provide a choice b/w
prompt treatment or deferral
8. DRC – HIGH RISK CHARCTERISTICS
(6)
1. Presence of Vitreous/ pre-retinal haemorrhage
2. Presence of new vessels
3. NVD – New vessels on or within 1 DD of Optic disc
4. Severe new vessels ( NVD >1/3 disk area or NVE >1/2 disk area)
10. ETDRS – INTRODUCTION (1)
• DRS – did NOT
• Address the question of timing or extent of PRP in DR
• Clarify role of Laser photocoagulation in NPDR and early PDR
• ETDRS – multicentre, randomized clinical trial, designed to evaluate
argon laser photocoagulation and aspirin treatment in management
of NPDR or early PDR
• 3711 patients recruited, minimum of 4 years follow up
• Recruitment began in December 1979 and was completed in July
1985
11. ETDRS – PURPOSE (2)
•To evaluate the effectiveness of argon laser photocoagulation and in
delaying or preventing progression of early DR to more severe stages
of visual loss and blindness
•To help determine the best time to initiate PRP in DR
•To determine if photocoagulation is effective in management of DME
•To evaluate the effectiveness of aspirin treatment in altering the
course
12. ETDRS – STUDY PATTERN (3)
Patient eyes
randomized
One eye
Immediate
photocoagulation
Other eye
Deferral of
photocoagulation
(careful Follow up)
(until high risk PDR
developed)
DME
Immediate
photocoagulation
Focal leaks -
Focal
Diffuse leaks -
Grid
Deferred
Patients
Aspirin Placebo
Term
‘Clinically significant macular
edema’
coined
to designate this level of
severity
• Eligibility criteria – presence of mild to very severe NPDR and/or non high risk PDR with
or without macular edema in both eyes.
13. ETDRS - RESULTS (4)
•High-risk PDR –
• Both early scatter and deferral were followed by low rates of severe visual loss (5 year rates in
deferral subgroups were 2-10%; in early photocoagulation groups these rates were 2-6%).
• Statistically significant reduction in severe visual loss for eyes with early treatment, especially for
those patients with Type 2 DM. However, the reduction was small and the risk was low in the
deferral group.
•Macular Edema –
• ‘Less severe retinopathy’ – focal with delayed scatter, initiated only when more severe retinopathy
developed
• ‘More severe retinopathy’ – immediate focal + mild scatter
• Worst outcome strategy – immediate full-scatter photocoagulation & focal deferred
• Focal photocoagulation reduced the risk of moderate vision loss by 50% or more and increased the
chance of a small improvement in visual acuity, especially in eyes where the centre of macula was
involved or threatened
• Thickening involved or threated centre of macula – clear benefit of focal laser
• Visual prognosis worse for eyes with worse baseline vision, although magnitude of treatment benefit
increased as baseline VA decreased
• Fluorescein leakage – not a sufficient indication for laser treatment in absence of CSME. Observe at 4
monthly intervals
14. ETDRS - RESULTS (5)
•Visual fields – Significant visual loss occurred in immediate full scatter
subgroup
•Accommodative amplitude – Full scatter photocoagulation produced
transient reduction in accommodative amplitude
•Vitrectomy –
• Overall vitrectomy rate 5.6%
• Patients undergoing vitrectomy – white, type 1 DM, younger at onset of DM, more likely
to have proteinuria, higher HBA1c and severe NPDR or worse at baseline
• Visual outcome – not altered by treatment assigned to immediate or deferred
photocoagulation or by pre-operative presence of RD
•Aspirin – use did not affect the progression of retinopathy to the high-risk
proliferative stage but aspirin also did not increase the risk of vitreous
hemorrhage, did not affect vision, and was associated with a decreased risk
of cardiovascular disease.
15. ETDRS – CONCLUSION (5)
•Severe NPDR/ Early PDR – consider scatter treatment, especially for
Type 2 DM
•High Risk PDR – scatter treatment, without delay
•Mild to moderate NPDR with CSME – focal photocoagulation
•Severe NPDR/ PDR with CSME – focal photocoagulation
•Aspirin –
• no clinically important beneficial effect on progression of retinopathy in mild to
severe NPDR or early PDR
• No ocular contraindications to it for CVS or other medical indications
17. DCCT (1)
• Examined whether intensive treatment with the goal of maintaining
blood glucose concentrations close to normal range could decrease
the frequency and severity of complications of DM
• Multicentre study done from 1983 to 1993
• Done in USA
• Funded by National Institute of Diabetes and Digestive and Kidney
Diseases
• 1441 patients with Type 1 DM
18. DCCT – PURPOSE (2)
• To assess the effect of tight glycaemic control on complications of
diabetes (nephropathy, neuropathy and diabetic retinopathy) for
persons with Type 1 DM
19. DCCT – STUDY PATTERN (3)
Type 1 Insulin Dependent Diabetes
Mellitus Age 13–39 years patients
randomized to Conventional
Treatment or Intensive Treatment
Group
Inclusion Criteria
Primary –
prevention
cohort
Secondary –
intervention
cohort
Type 1 DM 1-5 years 1-15 years
DR grade No
retinopathy
Mild to
moderate
NPDR
Urinary
albumin
excretion
(mg/24
hours)
<40 <200
Exclusion Criteria
• Hypertension
• Hypercholesterolemia
• Severe diabetic complications or
medical conditions
1 or 2 daily
insulin
injections
External insulin pump or >3
daily insulin injections,
guided by frequent blood
glucose monitoring
20. DCCT – RESULTS (4)
Primary Prevention Cohort Secondary Intervention Cohort
Intensive
therapy
Reduced risk of development
of DR by 76% in comparison
to other group
Slowed progression of DR by
54%
Reduced development of PDR or
severe NPDR by 47%
Intensive therapy reduced occurrence of
• Microalbuminuria by 39%
• Albuminuria by 54%
• Clinical nephropathy by 60%
21. DCCT – CONCLUSION (5)
Intensive therapy effectively delays onset and slows progression of
microvascular complications of diabetes – DR, nephropathy and
neuropathy in patients with Type 1 DM
23. UKPDS (1)
• Done to determine whether improved blood glucose control in Type
2 diabetics would prevent complications of DM
• Multicentre, randomized controlled trial
• 5102 people with newly diagnosed Type 2 DM
• UK
• 1977 – 1991
24. UKPDS (2)
Purpose
To determine whether the risk of CVS and microvascular complications in type 2
DM can be reduced by intensive control of Blood glucose
In patients with high BP, to determine whether the risk of complications can be
reduced by tight control of BP
To determine if any specific measurement for type 2 DM confers any particular
benefit
Study Pattern
Inclusion criteria – newly diagnosed type 2 DM
Outcome measure – follow up of patients to major fatal and non-fatal clinical end
points
25. UKPDS (3)
Result
• For every percentage point decrease in HbA1C (e.g.9% to 8%), there was a 35%
reduction in the risk of microvascular complications of disease
• More intensive blood pressure control resulted in a 37% reduction in microvascular
complications of DM
Conclusion
• Complications of DM can be reduced by improving blood glucose and/or BP,
greatest effect being on microvascular complications
27. DRVS (1)
• Done with view that it was important to determine whether early
vitrectomy had a better visual outcome or instead produced a rate of
serious complications higher than the rate associated with
conventional management in patients vitreous haemorrhage
• October 1976 – June 1983
28. DRVS – PURPOSE (2)
• To compare two therapies, early vitrectomy and conventional
management for recent severe vitreous haemorrhage secondary to DR
•To compare early vitrectomy and conventional management in eyes
that have good vision but a poor prognosis, because they are
threatened with haemorrhage or retinal detachment from very severe
PDR
•To study natural history of severe PDR
Conventional management – included vitrectomy if haemorrhage failed
to clear during a waiting period of 6 – 12 months or if retinal
detachment involving the centre of macula developed at any time
29. DRVS– STUDY PATTERN (3)
Inclusion criteria –
• At least 1 eye with severe VH & VA <5/200
• Extensive active neo-vascular or fibro-vascular proliferations & VA > 10/200
Outcome measure
• Primary outcome – VA
• ‘Good vision’ – VA >10/20
• ‘Poor vison’ – VA <5/200
30. DRVS – CONCLUSION (4)
•Recent severe VH causing significant reduction of vision Early
vitrectomy (especially in Type 1 diabetics and if VA is poor in fellow
eye)
•Severe, active neo-vascular proliferation & moderate/ no VH – Early
vitrectomy (especially in those with both fibrous proliferations and at
least moderately severe vessels, in which extensive scatter
photocoagulation has been carried out or precluded by VH)
31. DRVS (5)
•Results of DRVS – obtained before development of modern vitrectomy
instrumentation, techniques and endo-laser photocoagulation. With
these techniques, results are more favourable
•Nowadays in general – Recommended timing of vitrectomy for severe
diabetic VH is before 3 months for Type 1 diabetics and 6 months for
Type 2 patients.
33. DRCR.NET
A collaborative network dedicated to facilitating multicentre clinical
research of DR, DME and associated conditions
Formed in September 2002
Funded by National Eye Institute
34. PROTOCOL A: PILOT STUDY OF
LASER PHOTOCOAGULATION FOR
DME
Purpose
• To compare 2 laser photocoagulation
techniques for treatment of DME : modified
ETDRS (mETDRS) technique and mild macular
grid (MMG) technique
Methods
• Patients randomized into 2 treatment groups
• MMG burns –
lighter, more diffuse in nature & distributed throughout
macula in both areas of thickened and unthickened
retina
Microaneursysms - NOT directly photocoagulated
• mETDRS direct/ grid photocoagulation –
treats only thickened retina, areas of retinal non-
perfusion & leaking microaneursyms
Modification to ETDRS protocol – burns are less intense
(gray) and smaller (50 µ)
• VA, fundus photographs, OCT – taken at 3, 5,
8, 12 months
• Main outcome measure – change in OCT
measures at 12 months
Results
• From baseline to 12 months CMT (central
subfield thickening) decreased by an average
of 88µ in mETDRS group & 49µ in MMG group
• At 12 months mean change in VA was 0
letters in mETDRS group & 2 letters worse in
MMG group
Conclusion
• At 12 months of treatment, MMG less effective
than mETDRS at reducing retinal thickening.
• However, VA same b/w 2 groups
Application to Clinical Practice
• mETDRS photocoagulation should continue as
standard approach for treating DME
35. PROTOCOL B: RANDOMIZED TRIAL
COMPARING IVTA AND LASER
PHOTOCOAGULATION FOR DME
Purpose
• To evaluate of efficacy and
safety of 1 mg and 4 mg
dose of IVTA in comparison
with focal/ grid
photocoagulation (LP) for
DME
Methods
• Eyes randomized into 3
groups – LP, 1 mg IVTA & 4
mg IVTA
• Retreatment given for
persistent or new edema – 4
months intervals
• Outcome measures – ETDRS
VA, OCT – macular thickness
and safety at 3 years
Results
• 4 months mean VA better in 4 mg IVTA group than other
2 groups
• 1 year no significant differences among groups
• OCT results – same as VA results
• IOP increase and cataract surgery being performed 4 mg
IVTA > 1mg IVTA > LP
Conclusion
• Over 2- 3 years LP more effective, lesser side effects
• Most eyes receiving 4 mg IVTA likely to require cataract
surgery
• 4 mg IVTA – did reduce progression of DR, but its use not
warranted
Application to Clinical Practice
• Focal/ grid photocoagulation – benchmark for treatment of
36. PROTOCOL C: TEMPORAL
VARIATION IN OCT
MEASUREMENTS OF DME
Clinical impact of diurnal variation of macular edema is likely to be
small and not significant
37. PROTOCOL D: EVALUATION OF
VITRECTOMY FOR DME
Vitrectomy performed for eyes with at least moderate vision loss and
VMT usually result in a reduction in macular thickening
VA results are less consistent with some eyes improving and some
eyes worsening
38. PROTOCOL E: RANDOMIZED TRIAL OF
PERIBULBAR TRIAMCINOLONE
ACETONIDE (TA) WITH AND WITHOUT
FOCAL PHOTOCOAGULATION FOR MILD
DME – PILOT STUDY
Unlikely that significant clinical benefit exists for TA in cases of DME
with good VA
39. PROTOCOL F: OBSERVATIONAL
STUDY OF DEVELOPMENT OF DME
FOLLOWING SCATTER LP
PRP for DR can be safely administered in a single sitting in patients
with relatively good VA and no or mild pre-existing center involved
DME
41. PROTOCOL H: PHASE 2 RANDOMIZED
CLINICAL TRIAD OF INTRAVITREAL
BEVACIZUMAB (IVB) FOR DME
Results demonstrated that IVB can reduce DME in some eyes, but
study was not designed to determine whether treatment was
beneficial
42. PROTOCOL I: LASER-RANIBIZUMAB-
TRIAMCINOLONE STUDY FOR DME
PURPOSE
To evaluate intravitreal 0.5 mg Ranibizumab or 4 mg
Triamcinolone combined with focal/grid laser
compared with focal/grid laser alone for treatment of
DME
METHODS
Multicentre, randomized clinical trial enrolled a total
of 854 eyes of 691 participants with VA of 20/321 to
20/320 and DME involving the fovea
Retreatment followed an algorithm facilitated by a web
based design
Main outcome measures – BCVA and safety at 1 year
RESULTS
1 year mean change in VA from baseline – significantly
greater in ranibizumab + prompt laser group and
ranibizumab + deferred laser group, but not in
Triamcinolone + laser group compared with sham +
prompt laser group. 2 year VA similar to 1 year
outcomes
Reduction in mean CMT in triamcinolone + prompt
laser group similar to both ranibizumab groups and
greater than in sham + prompt laser group
3 eyes (0.8%) had injection-related endophthalmitis in
Ranibizumab groups
Elevated IOP and cataract surgery – more frequent in
Trimacinolone + prompt laser group
CONCLUSION
Intravitreal ranibizumab with prompt or deferred laser
– more effective at 2 years compared with prompt
laser alone for treatment of DME involving central
macula
Pseudophakic eyes – IVTA + prompt laser – more
effective than laser alone, but frequently with the risk
of IOP elevation.
APPLICATION TO CLINICAL PRACTICE
Ranibizumab should be considered for patients with
DME including vision impairment with DME involving
centre of macula
Eyes - Randomized
Sham injection +
prompt laser (n=293)
0.5 mg Ranibizumab
+ prompt laser
(n=187)
0.5 mg Ranibizumab
+ deferred laser (>24
weeks) (n =188)
4 mg Triamcinolone +
prompt laser (n=186)
43. PROTOCOL J: LASER-
RANIBIZUMAB-TRIAMCINOLONE
STUDY FOR DME + PRP
Risk of short term exacerbation of macular edema and associated VA
loss following prompt PRP in eyes also receiving focal/grid laser for
DME – can be reduced by IVTA or Ranibizumab
44. PROTOCOL K: THE COURSE OF
RESPONSE OF FOCAL
PHOTOCOAGULATION FOR DME
PURPOSE
To determine whether eyes with centre involved DME, treated with LP , in which there is a reduction in CMT measured
with OCT after 16 weeks
METHODS
Prospective, multicentre, observational single group LP study of 122 eyes with centre involved DME (OCT CMT>250µ)
At 16 weeks, continuing every 8 weeks - eyes assessed for retreatment
Additional laser deferred – if VA score improved >5 letter or OCT CMT decreased >10% compared with visit 16 weeks
prior
RESULTS
115 eyes completed 16 week visit
AT 16 weeks 47% (54) had decreased CMT by >10% compared with baseline
Of these, 48% (26) had CMT>250µ at 16 weeks, and were evaluable at 32 weeks
11 of 26 eyes – further decrease in CMT >10% from 16 to 32 weeks without further treatment
CONCLUSION
16 weeks following LP for DME, in eyes with definite reduction, but not resolution, of central edema, 23-63% will
continue to improve without additional treatment
APPLICATION TO CLINICAL PRACTICE
Eyes undergoing focal/ grid laser, especially eyes with greater macular thickening may continue to have improvement in
VA and macular thickness even after 16 weeks
45. DRCR.NET - COMPARATIVE
EFFECTIVENESS STUDY OF
AFLIBERCEPT, BEVACIZUMAB, OR
RANIBIZUMAB FOR DME –
BACKGROUND (1)•Diabetic macular edema (DME) affects ~750,000 people in USA
•Intravitreous anti-vascular endothelial growth factor (anti-VEGF) injections of either aflibercept
(EYLEA), bevacizumab (Avastin), or ranibizumab (Lucentis) are effective in treating DME
•Relative efficacy and safety of these agents within a head-to-head study were unknown prior to
the results of this trial
•Aflibercept and ranibizumab are FDA approved for DME treatment
•Bevacizumab is not FDA approved for intraocular use
• used “off-label” for DME treatment
• repackaged into aliquots ~1/500 of systemic dose in cancer treatments
•Medicare allowable charges
• Aflibercept (2.0 mg): $1961
• Bevacizumab (repackaged 1.25mg): $67
• Ranibizumab (0.3 mg): $1189
46. DRCR.NET - COMPARATIVE
EFFECTIVENESS STUDY OF
AFLIBERCEPT, BEVACIZUMAB, OR
RANIBIZUMAB FOR DME –
PURPOSE(2)Primary Objective – For eyes with centre involved DME with
decreased VA, compare one year efficacy and safety of –
1. Intravitreal aflibercept (EYILEA)
2. Intravitreal Bevacizumab (AVASTIN)
3. Intravitreal Ranibizumab (LUCENTIS)
47. DRCR.NET - COMPARATIVE
EFFECTIVENESS STUDY OF
AFLIBERCEPT, BEVACIZUMAB, OR
RANIBIZUMAB FOR DME – STUDY
DESIGN (3)
47
Participants meeting all of the following criteria:
• At least 18 years old
• Type 1 or type 2 diabetes
Study eye meeting all of the following criteria:
• ~Snellen equivalent visual acuity 20/32 or worse and 20/320 or
better
• Central-involved DME on clinical exam
• Central subfield (CSF) thickness ≥ protocol-defined gender and
optical coherence tomography (OCT) machine-specific
thresholds
• No history of an anti-VEGF treatment for DME in the past 12
months or any other DME treatment in the past 4 months
Randomized, multi-center clinical trial (N = 89 Sites)
Primary Outcome: Change in visual acuity at one year adjusted for
baseline visual acuity using the intent-to-treat principle
Eyes
Randomized
( n=660)
Aflibercept 2.0mg
Bevacizumab 1.25mg
Ranibizumab 0.3mg
48. DRCR.NET - COMPARATIVE
EFFECTIVENESS STUDY OF
AFLIBERCEPT, BEVACIZUMAB, OR
RANIBIZUMAB FOR DME (4)
TREATMENT SCHEDULE
Repeat injections at every 4 week visit if eye improved or worsened
Otherwise defer injections if either
Visual acuity 20/20 or better and OCT CST “normal” or,
At or after 24 weeks, visual acuity and OCT stable after 2 consecutive injections
Resume injection if VA or OCT worsened
Improved/ worsened defined as –
≥ 5 letter change (~1 Snellen line) from last injection, or,
≥ 10% CST change on OCT from last injection
Focal/grid laser – initiated at or after 24 weeks only if persistent DME not improving
after at least 2 injections
49. DRCR.NET - COMPARATIVE
EFFECTIVENESS STUDY OF
AFLIBERCEPT, BEVACIZUMAB, OR
RANIBIZUMAB FOR DME – RESULTS
(5)All three anti-VEGF agents, on average, produced substantial visual acuity
improvement by 1 month, sustained through 1 year.
On average, greater improvement occurred with aflibercept, but relative
effect varied by initial visual acuity.
Mild initial vision loss (20/32-20/40, 50% of study eyes): little difference in mean visual acuity at
1 year
Worse initial vision loss: aflibercept had an advantage over the other agents
Bevacizumab had a lesser effect on reducing macular edema than the other two
agents, regardless of starting acuity.
Few eyes in any group had substantial visual acuity loss.
Median number of injections: 9 to 10 in all three groups.
Fewer eyes in the aflibercept group received focal/grid laser for DME after 24
weeks, presumably because a greater % of eyes in the aflibercept group had
resolution of central DME (which drives decision to apply laser).
50. DRCR.NET - COMPARATIVE
EFFECTIVENESS STUDY OF
AFLIBERCEPT, BEVACIZUMAB, OR
RANIBIZUMAB FOR DME – RESULTS
(6)Serious adverse event, death, and hospitalization rates appeared similar
among treatment groups.
Significant differences in frequencies of major cardiovascular events were
not identified
However, post-hoc analysis combining MedDRA system organ classes of cardiac and
vascular resulted in more participants in the ranibizumab group reporting these adverse
events.
This is inconsistent with prior studies and may be due to chance.
Endophthalmitis was rare: 0.02% of injections.
No differences in intraocular inflammation.
Bevacizumab:
Note: a central pharmacy repackaged into single use vials
• Testing was completed for sterility, purity, and potency, a standard that may not be available in a clinical practice
setting
Results may not apply to eyes with persistent or recurrent DME already receiving anti-VEGF
51. DRCR.NET - COMPARATIVE
EFFECTIVENESS STUDY OF
AFLIBERCEPT, BEVACIZUMAB, OR
RANIBIZUMAB FOR DME –
CONCLUSION (7)•All three anti-VEGF agents are effective treatments for DME
causing vision impairment.
•When initial visual acuity loss is mild, on average there is little
difference in visual acuity at 1-year.
•At worse levels of initial visual acuity aflibercept is more
effective at improving vision.
52. OTHER IMPORTANT CONCLUSIONS
OF DRCR.NET
1. Decline in Best Corrected ETDRS VA after dilatation in diabetic
subjects. Therefore, post dilatation ETDRS VA should not be used
2. Modest co-relation of OCT measured centre point thickness with
VA, modest correlation of changes in retinal thickening and VA
following focal laser treatment for DME.
3. CMT (central subfield mean thickness) is preferred OCT
measurement.
4. Low of endophthalmitis (for intravitreal injections) can be achieved
using topical povidone iodine, use of a sterile lid speculum and
topic anaesthetic, but does not require topical antibiotics
5. Transformation of OCT retinal thickness data to logOCT may assist
in assessment of clinically meaningful changes in retinal thickness