Biomedical Engineering Reference
In-Depth Information
concentrations are typically included in toxicity studies. IOP
reduction should not be a primary endpoint in a toxicity study but
instead IOP should be measured only to demonstrate that a toxico-
logically adverse alteration in IOP did not occur. Because it is easy to
identify these marked alterations in IOP, extensive predose, and
dosing phase assessments of IOP are not required. Additionally,
the large number of potentially confounding end-points required
in a toxicity study can frequently create so much “noise” in IOP
values that even a clinically meaningful reduction can be masked,
thereby creating confusion as to whether the test article actually
lowers IOP or not.
Endpoints meriting consideration in toxicity studies of
anti-glaucoma drugs include Hackett-McDonald or McDonald-
Shaddock ocular irritation scoring (which involve the application
of fluorescein stain and a topical mydriatic), corneal pachymetry,
anterior segment optical coherence tomography to evaluate
changes in corneal thickness and anterior segment morphology,
noncontact specular microscopy to measure corneal thickness and
assess changes in the corneal endothelium, gonioscopy, electroreti-
nography to assess retinal effects, electrocardiography, and systemic
blood pressure changes, a wide range of toxicokinetic samples and
histopathology of the eye and other organs.
References
1. Miller PE (2013) The glaucomas. In: Maggs
DJ, Miller PE, Ofri R (eds) Slatter's funda-
mentals of veterinary ophthalmology, 5th
edn. Elsevier, St. Louis, MO
2. Casson RJ, Chidlow G, Wood JP et al (2012)
Definition of glaucoma: clinical and experi-
mental concepts. Clin Experiment Ophthal-
mol 40(4):341-349. doi:
10.1111/j.1442-
9071.2012.02773.x
3. Nickells RW, Howell GR, Soto I et al (2012)
Under pressure: cellular and molecular
responses during glaucoma, a common neu-
rodegeneration with axonopathy. Annu Rev
Neurosci
7. Resnikoff S, Pascolini D, Etya'ale D et al
(2004) Global data on visual impairment in
2002. Bull World Health Organ 82:844-851
8. Collaborative Normal-Tension Glaucoma
Study Group (1998) Comparison of glauco-
matous progression between untreated
patients with normal-tension glaucoma and
patients with therapeutically reduced intraoc-
ular
pressures.
Am J Ophthalmol
126:487-497
9. The AGIS Investigators (2000) The advanced
glaucoma intervention study (AGIS):7. The
relationship between control of intraocular
pressure and visual field deterioration. Am J
Ophthalmol 130:429-440
10. Goel M, Picciani RG, Lee RK et al (2010)
Aqueous humor dynamics: a review. Open
Ophthalmol
35:153-179.
doi:
10.1146/
annurev.neuro.051508.135728
4. Klein BE, Klein R, Sponsel WE et al (1992)
Prevalence of glaucoma: the Beaver Dam Eye
study. Ophthalmology 99(10):1499-1504
5. Quigley HA, Broman A (2006) The number
of persons with glaucoma worldwide in 2010
and 2020. Br J Ophthalmol 90:151-156
6. Rudnicka AR, Mt-Isa S, Owen CG et al
(2006) Variations in primary open-angle glau-
coma prevalence by age, gender, and race: a
Bayesian meta-analysis. Invest Ophthalmol
Vis Sci 47(10):4254-4261
J
4:52-59.
doi:
10.2174/
1874364101004010052
11. Brubaker RF (2004) Goldmann's equation
and clinical measures of aqueous dynamics.
Exp Eye Res 78(3):633-637
12. Johnson TV, Tomarev SI (2010) Rodent
models of glaucoma. Brain Res Bull 81
(2-3):349-358. doi:
10.1016/j.brainresbull.
2009.04.004
