Sunday, June 30, 2019

CONTINUING MEDICAL EDUCATION: ONLINE  COURSES




As ophthalmologists we need to keep in touch with knowledge, either gained previously during our education and experience or to enhance and attain new information by studying books and journals, attending seminars and conferences, consulting experts of the particular field and visiting websites dedicated as information portals. However, often our focus during these interactions tends to waver, especially if the topic being discussed is either not of our interest or beyond our understanding of the subject. A talk on strabismus would most probably put me to sleep, as it is a topic which hardly interests me.


Therefore, we need to gain knowledge and test ourselves to be sure that we have indeed grasped the topic we are studying. In this context is the concept of Continuing Medical Education (CME). This is a quantum jump in the way we had been attaining knowledge after the completion of our post-graduate or specialty course. By insisting on compulsory CME points many organizations are improving the professional health of doctors.

It is the knowledge that we have gained which reflects in the manner we manage our patients and our interactions with others.
A prescription reflects your education and experience

A good way to participate in CME related activities is to enroll for online courses. This post takes a look at some free-to-access online CME and certificate courses which could benefit our community. 

Disclaimer: I did not personally check each website and not sure if it’s free-to-access.




Cybersight:

This website is powered by Orbis and has a number of online courses available for free. There is only one course dedicated to glaucoma.

https://cybersight.org/online-learning/


International Council of Ophthalmology:

ICO also has a page on its website where CME related information is available.

http://www.icoph.org/refocusing_education/educational_programs/e_learning.html


International Centre for Eye Health:

ICEH of the London School of Hygiene and Tropical Medicine has a large number of courses available on its website.

The Open Education for Eye Health program has developed a series of open online courses in key topics in public health eye care. The courses are free to access and the course material published under a non-restrictive Creative Commons license as Open Educational Resources (OERs).

https://iceh.lshtm.ac.uk/oer/


CMEList:

This website provides links to a number of online CME courses.

https://www.cmelist.com/free-ophthalmology-cme/


Medscape:

This popular website also has CME activities related to Ophthalmology .

https://www.medscape.org/ophthalmology


FutureLearn:

This is a very good portal which provides links to many online courses in all subjects.

https://www.futurelearn.com/


IJCAHPO:

EyeCare provides online courses for the allied/para-medical staff and other technicians related to Ophthalmic assisting.

https://eyecarece.jcahpo.org/EyeCareCE/EyeCareCEHome.aspx


Lions Aravind Institute of Community Ophthalmology:

India’s premier ophthalmic group, Aravind Eye Care System, through its knowledge portal: LAICO provides online courses for the entire Ophthalmic team.

http://www.aurosiksha.org/







Thursday, June 27, 2019

NEUROPROTECTION


GUEST AUTHOR

ZEBA SALEEM

AJMAL KHAN TIBBIYA COLLEGE
ALIGARH





INTRODUCTION

  • Glaucoma is a multifactorial neurodegenerative disorder. There is chronic loss of retinal ganglion cells (RGCs) and their axons in this condition. It is hoped that interventions involving neuromodulation (preserving neuronal structure/function), neuroprotection (preventing further neuronal damage) and neuro-regeneration (re-growth of damaged cells/neurons) could be utilized to manage this fearfully blinding disease. 
  • Neuroprotection in glaucoma refers to any intervention intended to protect the optic nerve or prevent the death of RGCs, in addition to and as a separate effect from lowering of IOP. 
  • This blog post reviews the pharmacological basis of neuroprotection in glaucoma.



PHARMACOLOGICAL APPROACHES TO NEUROPROTECTION

NMDA receptor antagonists:

  • Excess glutamate leads to NMDA receptor overactivity and excitotoxicity.
  • Initial experiments involved MK-801 (Dizocilpine).
  • It completely blocks normal glutamatergic neurotransmission (required for normal CNS function).
  • Experiments have shown MK-801 to be neuroprotective by decreasing expression of Bad and transient deactivation of the pro-survival kinase Akt pathway.
  • However, since MK-801 is a non-specific blocker of glutamatergic neurotransmission it is not appropriate for clinical use. 
  • Memantine is a non-competitive, low-affinity open channel NMDA blocker.
  • It exhibits selective blockade of excessively open channels with a fast off-rate.
  • It inhibits excessive NMDA receptor activity, while maintaining neoronal cell function.
  • It does not accumulate significantly within the channel.
  • However, a phase 3 clinical trial on memantine in OAG did not meet its primary end point.



Neurotrophic factors:

  • Experimentally neurotrophic factors such as BDNF and CNTF have been reported to enhance survival of RGCs (in optic nerve crush injury models).
  • A combination of BDNF and LINGO-1 antagonist has been experimentally shown to enhance long term RGC viability.
  • In vitro application of BDNF to isolated RGCs prolongs their survival. In vivo RGC survival is also found to be prolonged by intravitreal injection of BDNF.



Anti-apoptotic agents:

  • Supplements of creatine, alpha-Lipoic acid, nicotinamide and epigallocatechin-gallate (EGCG) act by countering oxidative stress, promote mitochondrial function and confer neuroprotection.
  • Inhibition of apoptosis can be achieved by 2 mechanisms=


  1. Activation of anti-apoptotic extracellular signal regulated kinase (ERK) and Akt by Brimonidine. These enhance the production of Bcl-2 and Bcl-xL.
  2. Blocking of apoptotic machinery by the use of caspase inhibitors. Caspases are a family of aspartate-specific cysteine proteases. The term caspase denotes the Cysteine requiring ASPartate proteASE activity of these enzymes.


  • Calpeptin, a calpain-specific inhibitor, has been studied for its role in neuroprotection. It prevents Ca++ influx, proteolytic activities and apoptosis in RGC cells.



Nitric oxide synthase antagonists:

  • NOS inhibitors such as 2-aminoguanidine, I-NOS and L-N6-(1-iminoethyl) lysine 5-tetrazole amide have been studied for their neuroprotective role.
  • Nipradiol, a beta- and alpha1- antagonist was also found to be neuroprotective.
  • However, others have reported an absence of NOS release by astrocytes and did not find any neuroprotective effect of amino-guanidine.



Anti-oxidants:

  • Anti-oxidants and free radical scavengers reduce RGC death occurring from NMDA toxicity.
  • Vitamins C, E, superoxide dismutase, catalase, Ginkgo biloba (EGb 761) have been shown to have these properties.
  • Ginkgo biloba also preserves mitochondrial metabolism and enhances ATP production in various tissues.



Calcium channel blockers:

  • Nifedipine and Verapamil confer neuroprotection by enhancing OBF. They also improve glutamate metabolism and are responsible for homeostasis in the ONH.
  • On the downside, these Ca++ channel blockers cause systemic hypotension which may aggravate retinal ischemia.
  • In a rat model, continuous treatment with candesartan (angiotensin II type I receptor blocker) provided significant neuroprotection.



Gene therapy:

  • Deprenyl (a monoamine oxidase inhibitor) increases gene expression of factors that halt apoptosis.
  • Flunarizine and aurintricarboxylic acid were found to retard apoptosis following light-induced photoreceptor cell death.



Immunomodulators and vaccination:

  • Glaucoma can be regarded as an immunogenic mechanism with prominent activation of resident and systemic immune responses during the early course of the disease. 
  • Chronic glial activation is regarded as a hallmark of neuroinflammation in glaucoma.
  • Associated failure in regulation of immune response pathways may lead to a neurodegenerative state and promote injury to neurons.
  • Adaptive/protective responses of resident or systemic immune cells can support neurons and promote tissue repair mechanisms after injurious insults.
  • Glatiramer acetate= A non-biological complex heterogeneous mixture of synthetic polypeptides. Peptide epitopes in Glatiramer acetate compete with autoantigens for binding with major histocompatibility complex molecules or antigen-presenting cells, thereby altering the functional outcome of T-cells signaling from inflammatory to anti-inflammatory responses.
  • Pharmaceutical inhibition of TNF-a, a major pro-inflammatory and pro-apoptotic cytokine has provided protection against RGC and axonal degeneration in experimental models of glaucoma.
  • Selective inhibition of TLR4 signaling with  TAK-242 (resatorvid) has been found to reduce astrocyte activation and RGC death after ON crush injury in mice.
  • Inactivation of astroglial NF-kB the key transcriptional activator of inflammatory mediators downstream of TNF-a/TNFR and TLR signaling pathways has reduced the pro-inflammatory genes and promoted RGC survival after retinal ischemia.
  • Intraocular administration of cAMP phosphodiesterase inhibitor (Ibudilast) has resulted in decreased production of pro-Iflammatory mediators and increased survival of neurons in Ocular hypertensive rat eyes.



Geranylgeranylacetone (GGA):

  • GGA has been observed to evoke the synthesis of HDP70, this could have a neuroprotective role.



Stem cell therapies:

  • Stem cells are thought to exert neuroprotective effects by generating neurotrophic factors, modulating MMP and other aspects of the CNS environment that may promote endogenous healing.
  • Granulocyte-Colony stimulating factor (G-CSF) is greatly expressed by RGCs and may provide neuroprotection.
  • Oligodendrocyte precursor cells (OPCs), a type of neural stem cell, may provide protection to RGCs.
  • Mesenchymal stem-cell derived exosomes have been reported to deliver trophic and immunomodulatory factors, suppress the migration of inflammatory cells, attenuate pro-inflammatory cytokine secretion and promote RGC survival. 



Bioenergetics:

  • It is the study related to metabolic processes  leading to energy utilization in the form of ATP molecules.
  • Energy failure and mitochondrial dysfunction in the ONH may have a role in glaucoma due to reduced energy and increased free radical production.
  • Enhanced mitochondrial function or increasing energy supply of neurons may provide neuroprotection.



Sunday, June 16, 2019

MALIGNANT GLAUCOMA


Guest author
NAZMI USMANI
Ajmal Khan Tibbiya College
Aligarh
India




Introduction:

It is also known as:
Aqueous misdirection syndrome
Ciliary block glaucoma
Cilio-lenticular block
or Direct lens block glaucoma


The term “malignant glaucoma” was used by Von Graefe (1869) for a condition characterized by: “A shallow or flat anterior chamber with an inappropriately high intraocular pressure (IOP), despite a patent iridectomy”. 

As it was a violent form of secondary glaucoma (especially in the post-operative setting), that was resistant to treatment and often resulted in blindness (poor prognostic outlook), it was termed “malignant”.

It is regarded as a multifactorial condition that is thought to occur in anatomically predisposed eyes.

Etiology:
It may occur in phakic, pseudophakic or aphakic eyes.

It can occur following:
  • Glaucoma filtering surgery (GFS) [especially in angle closure eyes].
  • Other surgeries, such as: cataract surgery (with or without intra-ocular lens), scleral buckle, pars plana vitrectomy.
  • Laser procedures: Nd:YAG cyclophotocoagulation, after laser-iridotomy or -sclerotomy 
  • Implantation of a large optic intra-ocular lens (>7 mm).
  • Use of miotics in predisposed eyes.

Idiopathic cases of malignant glaucoma (MG) have also been reported.

Prevalence:
2-4% angle closure glaucoma patients undergoing GFS develop malignant glaucoma.
2.3% post-keratoplasty patients and 1.3% patients who undergo GFS alone or combined with cataract extraction develop MG.
Females have 3 times higher risk of developing MG, as compared to men (apparently due to smaller ocular dimensions).

Predisposing factors:
  • Axial hyperopia
  • Nanophthalmos
  • Chronic angle closure with plateau iris configuration 
  • H/O malignant glaucoma in fellow eye
  • A thick sclera may cause partial stenosis of vortex veins, impairing normal venous outflow and cause engorgement of choroid. Opening of anterior chamber during surgery lowers IOP suddenly with forward movement of the lens-iris diaphragm. This triggers MG in these eyes.
  • A lens which is too large for the eye (disproportion between the volumes of the lens and eyeball predispose the eye to MG). The choroid gets edematous due to accumulation of blood when outflow is impaired. The ciliary body and iris rotate to the front closing access to the filtration angle from the back.
  • In nanophthalmos the lens is larger in volume; there is decreased axial length and thickened choroido-scleral layer. This causes crowding of the anterior segment.
  • A peripheral iridotomy does not prevent overfilling of the choroid (which leads to progressive angle closure).
  • Eyes predisposed to develop MG have connective tissue related pathologies and accumulation of glycosaminoglycans in the vitreous.

  
Pathogenesis:

There are different theories which explain the development of malignant glaucoma=

I. Schaffer and Hoskins theory (“Posterior pooling of aqueous”): Aqueous flow is diverted posteriorly causing pooling (accumulation) of aqueous behind a posterior vitreous detachment. This shifts the lens-iris diaphragm anteriorly causing a pupillary block.

II. Chandler and Grant theory (“Slackness of lens zonules”): Laxity of lens zonules coupled with positive vitreous pressure causes a forward movement of lens. This sets up a vicious cycle in which the higher the pressure in the posterior segment, the more firmly is the lens pushed forward.

III. Quigley et al. (“Choroidal expansion”): The precipitating event is choroidal expansion which increases vitreous pressure. The initial compensatory outflow of aqueous along the postero-anterior pressure gradient causes shallowing of the anterior chamber.

IV. Final common pathway:
Establishment of vicious cycle whereby the transvitreal pressure cannot be established by outflow of aqueous humor -> Fluid buildup behind the vitreous leads to vitreous condensation which exerts a forward force -> Anterior displacement of the lens-iris diaphragm 


Classification:

Classical malignant glaucoma: It is a rare complication of incisional surgery for primary angle-closure glaucoma. It is independent of the type of surgery and preoperative IOP. It can occur immediately after surgery to many years later. In the early postoperative period it is related to cessation of cycloplegic drugs. There is partial or total closure of the drainage angle at the time of surgery and axial hypermetropia is associated with increased risk of MG.

Nonphakic malignant glaucoma: Develops in patients after cataract extraction. It may occur with or without antecedent glaucoma.
   
Malignant glaucoma in aphakia
Malignant glaucoma in pseudophakia

Miotic induced malignant glaucoma: Perhaps associated with contraction of ciliary body or associated with forward shift of the lens leading to shallowing of anterior chamber. 

Others: Malignant glaucoma associated with bleb needling, infection and inflammation and other ocular disorders.

Spontaneous malignant glaucoma: MG may develop spontaneously in the absence of previous surgery, miotic therapy or any other apparent cause. 

Evaluation:

Medical history=
1. Determination of predisposing factors
2. Symptoms: Patients usually present with red, painful eye, decreased vision (similarly to pupillary-block glaucoma). Headache, nausea and vomiting may also occur, depending on IOP. Myopic shift related to anterior movement of lens-iris diaphragm, with secondary improvement of near vision occurs. Persistent symptoms due to anterior synechiae associated with long-standing shallowing of anterior chamber.

Slit-lamp examination:
Anterior chamber depth= Central & peripheral shallowing of the anterior chamber.
Patency of iridotomy should be examined. If none is visible, an iridotomy should be attempted.
Iris is not bowed anteriorly (iris bombe’ of Angle Closure Glaucoma)
Vitreous may have optically clear spaces. This can also be seen on B-scan ultrasound.
Seidel test should be performed to exclude filtering bleb leaking after filtration surgery. Such cases present with hypotony.
Posterior segment should be examined or assessed by ultrasound to rule out choroidal detachment or suprachoroidal hemorrhage.
Tonometry and gonioscopy should be performed.


Ultrasound Biomicroscopy (UBM):
Anterior rotation of ciliary processes, which press against the lens equator (or the anterior hyaloid in aphakia) and prevents forward flow of aqueous (hence the term ciliary block glaucoma). 
In some cases UBM has shown the size of the lens to be smaller than normal, that may allow the lens to move forward within the eye.


Differential diagnosis:
  1. Acute angle closure glaucoma: Anterior chamber depth is not uniform (centre deeper). Responds to peripheral iridotomy. 
  2. Choroidal detachment/effusion: Usually inflammatory in nature (trauma, following surgery, scleritis, chronic uveitis, Vogt-Koyanagi-Harada disease, following cyclo-photocoagulation/cryotherapy). IOP is normal or reduced. 
  3. Suprachoroidal hemorrhage: Shallowing of anterior chamber, increased IOP, sudden pain, hemorrhagic/non-serous detachment of the choroid. Usually occurs within one week of surgery.


Management:

Shallow AC beyond 5 days may cause formation of peripheral anterior synechiae, posterior synechiae, cataract and damage to corneal endothelium.
  • Medical
  • Laser
  • Surgery
  • Management of fellow eye


Hyperosmotic agents= 20% mannitol IV reduces the pressure exerted by vitreous (oral glycerol can also be substituted if mannitol is not available or contraindicated).

Mydriatic-cycloplegic= Combination therapy with 1% Atropine and 10% phenylephrine drops causes relaxation of ciliary muscle and tighten the zonules, pulling the anteriorly displaced lens backwards.

Aqueous suppressants= Beta-blockers or alpha2-agonists or carbonic anhydrase inhibitors are utilized to reduce the IOP.

Anti-inflammatory agents= Topical steroids are used to control the inflammation. 

Maintenance therapy= The patient is put on life-long atropine drops to prevent recurrence. Atropine can be instilled once every 4-6 weeks and every time patient notices any refractive change due to AC shallowing the treatment can be re-instituted. 

Miotics are contraindicated for life.

In case there is no response within 5 days, laser and/or surgery is employed.

Laser treatment= Nd-YAG laser hyaloidectomy, to disrupt the anterior vitreous face and establish proper flow of aqueous, can be undertaken in aphakic and pseudophakic eyes. (3-11 mJ energy). 

Argon laser for photocoagulation of the ciliary processes to destroy the ciliary processes and reduce aqueous production can be attempted. If not possible through an iridotomy, trans-scleral cyclphotocoagualtion can be done.

Surgery= When Medical or laser therapy fails surgical intervention is required. It involves vitrectomy to reduce the vitreous volume and promote aqueous flow into the anterior chamber. Usually a combination of posterior scelerectomy and air injection in the anterior chamber, anterior pars plana vitrectomy and lens extraction is done.

Prophylactic measures:

Cessation of miotic drops should be done as soon as possible.

Conclusion:

Malignant glaucoma is a therapeutic challenge.
Patients with H/O malignant glaucoma in fellow eye and PACG should be closely followed after glaucoma surgeries.
Patients have relatively good prognosis with current therapeutic modalities. More than 50% patients apparently respond to conservative management.