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T. Farra , M. Jacisin 1 2
1
Brigham and Womens Hospital, New England College of Optometry, Boston, MA 2

Introduction
Introduction Methods
Methods Results
Results--cont
cont Results
Results--cont
cont
Retinal ganglion cells (RGC) die by apoptosis in both high tension and
1 The sample was selected from patients aged 40 and older who The NTG group used significantly less steroids then the control group Table 2: Conditions/Procedures Included in the Allergic, Inflammatory and Ant Seg surg Categories.
Allergic Inflammatory Ant. Seg. Surgeries
low tension2 glaucoma. Ischemia and neuronal compression may presented to the Division of Ophthalmology at Brigham and Womens for all definitions of steroid exposure. Fig. 1 and 2 show the proportion Allergic Rhinitis Sarcoid *Cataract Extration (CE)
deprive the RGCs of essential trophic factors necessary for their Hospital from July 1998 to January 1999. Patients were required to of people taking steroids in the NTG and Control group for total steroid Atopic Dermatitis Crohns disease Trabeculectomy
use and steroid use excluding anterior segment surgery respectively. Eczema Graves disease CE with Trab
survival3. When apoptosis occurs, the RGC cytoplasmic volume have electronic medical records dating back to at least 1996. Hayfever Polymyalgia Rheumatica
decreases and the cell membrane ruptures, while the nucleus All patients were examined by a single observer. * indicates a statistically significant difference between the NTG and Systemic Lupus Erythematosis
condenses4. RGC membrane lysis is mediated by phospholipases and Each patient was questioned about their past ocular, medical and Control groups using 2. Unspecified granulomatous disease
Fig 2: Steroid Use excluding ocular surgery in
oxidative enzymes. Leaky RGC may release other toxic substances surgical history, as well as current use of medications. An extensive Fig 1: Steroid Use in NTG and Control groups NTG and Control groups Fig. 6 shows the proportion of different types of steroids used for
such as excitatory amino acids, which further damages neighboring history of past and present steroid use was obtained which included
cells3. Glutamate, an excitatory amino acid, has been found in elevated
Proportion of Steroid Users in NTG Proportion of Steroid Users in NTG systemic conditions by patients in the NTG and Control groups
and Control Groups
name of the steroid, dose, frequency of administration, duration, and and Control Groups - Excluding Ant
respectively. Table 3 indicates the specific steroids included in the
concentrations in the vitreous body of glaucomatous eyes 5. seg surgery
time period of use. Inhaler, Topical and Oral categories.
0.35
* *

Proprotion of Steroid
Subsequently, all patients underwent a complete eye examination. *
0.3 0.35
0.25 0.3
*

Steroid Users
* *

Proportion of
Steroids are known to be nonspecific blockers of cell membrane Any patient suspected of having glaucomatous optic neuropathy 0.2 0.25 Fig 6: Type of Steroids Used for systemic Table 3: Specific steroids included in the Inhaler,

Users
0.15 0.2
NTG 0.15 conditions in NTG and Control groups. Topical and Oral categories.
lipases6 which may inhibit apoptosis in this setting. Furthermore, based on the appearance of the optic nerve and nerve fiber layer 0.1
Control 0.1
NTG
0.05 0.05 Control NTG Control
certain glucocorticoids are thought to intercalate into the cell membrane underwent visual field testing with either the Humphrey or Goldmann 0 0 11%
21%
Steroid Steroid Steroid Steroid Steroid Steroid
and decrease neuronal and vascular membrane fluidity by inhibiting perimeters. Patients with unreliable visual fields or no reproducible Ever Before After 7/97 Ever Before After 7/97 Inhaler
7/97 7/97
oxygen free radical-induced lipid peroxidation 7. Studies have shown that visual field loss were excluded.
22%
Topical
Oral
RGC survival in vitro is dependent on the addition of steroids to the
58%
21%
67%

culture8. Logistic regression predicted the Odds ratio to be 0.517 Model A

Ophthalmic information regarding ocular conditions, surgeries and (p=0.07), 0.408 Model B (p=0.02), and 0.81 Model C (p>0.05) for the
maximum IOP was corroborated from the patients eye records. development of NTG. The Odds ratios are plotted in Fig. 3 for the 3
Finally there is data suggesting an immune deviation in patients with Non-ophthalmic information was confirmed by a review of the patients Models. Models A, B, and C are described in Table 2. Discussion
Discussion
NTG2 where serum antibodies directed to retinal elements have been electronic medical record. These records contained information
found. Exogenous steroids could prevent NTG by nonspecifically regarding the patients medical conditions, as well as the date of first The speculation that steroids may prevent apoptosis is plausible
blunting this aberrant response. and filled prescription for all medications.
based on their ability to inhibit cell membrane lysis mediated by
phospholipases and oxidative enzymes. In our study, univariate
Steroid exposure was defined as a dichotomous variable in three
analysis suggests that steroid use was associated with a reduced
Purpose
Purpose ways relative to July 1, 1997 (1 year prior to the onset of the study).
odds of having NTG.
Steroid use for a period of 1 month at any given time in the past.
Problems regarding confounding by indication make the univariate
Steroid use prior to July 1, 1997 for at least 1 month.
To study the association of steroid use and prevalence of NTG in a result of this study controversial. Larger scale prevalence studies
Steroid use after July 1, 1997 for at least 1 month.
clinic-based population. confirming our univariate finding are necessary. In these studies, very
careful estimate of steroid exposure would be indicated.
The Odds ratio for steroid use was calculated using logistic regression
Sample
Sample analysis for each definition of steroid use. The results were adjusted
for age, race, gender, hypertension, diabetes and diseases that were Fig 6: Type of Steroids Used for systemic Fig 6: Type of Steroids Used for systemic Conclusions
Conclusions
The sample consisted of 154 patients: indications for steroid use. conditions in NTG and Control groups. conditions in NTG and Control groups.

72 NTG (mean age 69.0 10; 44-85; 25M, 47F) Univariate logistic regression analysis demonstrates a reduced odds
82 controls (mean age 64.8 11; 44-86; 31M, 51F) Results
Results Cataract extraction was significantly higher in the Control group of NTG in steroid users.
compared to the NTG group. No difference was found in any systemic Controlling for age strengthens this association. Controlling by
Definition of NTG Cases The demographic and clinical characteristics of NTG and Control conditions between cases and controls. Fig. 4 and 5 show the indication for steroid use produces a result that is not statistically
Patients with ONH or NFL appearance consistent with glaucoma. groups is described in Table 1. breakdown of conditions requiring steroids in the NTG and Control significant.
Maximum IOP less then 21mmHg. group for systemic and ant. seg. ocular surgery respectively. Table 2 Larger numbers of cases and controls will be necessary to
At least two reliable visual field examinations with reproducible shows the conditions/procedures included in the Allergic, Inflammatory demonstrate the true relation between steroid use and NTG.
defects consistent with the nerve fiber layer pathology. and Total Ant. Seg. surgery categories. * indicates a statistically
Table 1: Demographic and Clinical Characteristics of NTG and Control groups. significant difference between the NTG and control groups using 2.
No evidence of exfoliation or trauma on slit lamp examination and no
evidence of an occludable angle or angle recession on gonioscopy.
NTG Control p-value References
References
Age 69 1.2 65 1.2 P=0.01 Fig 4: Breakdown of systemic conditions Fig 5: Breakdown of Ant. Seg. surgeries requiring
Patients with pre-existing iridotomies were excluded form the study. (mean sd) requiring steroids for NTG and Control steroids for NTG and Control groups.
groups. 1 Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ. Retinal ganglion cell death in
Female 66% 62% Proportion of People with Conditions experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 1995;36:774-
Requiring Steroid Use Proportion of People with Ant. Seg. 86.
Definition of Controls Race
Surgery Requiring Steroid Use 2 Wax MB, Tezel G, Edward PD. Clinical and ocular histopathological findings in a patient with normal-
White 55% 65%
No evidence of glaucomatous optic neuropathy: Black 30% 21%
0.35
0.3
pressure glaucoma. Arch Ophthalmol 1998; 116:993-1001.
3 Chew SJ, Ritch R. Neuroprotection: the next breakthrough in glaucoma? Proceedings of the Third
cup/disc ratios < 0.6 OU Hispanic 7% 5% 0.25 0.2
* Annual Optic Nerve Rescue and Restoration Think Tank. J Glaucoma 1997; 6:263-6.
0.2 NTG 4 Spaeth GL. Glaucoma, apoptosis, death, and life. Acta Ophthalmol Scand Suppl 1998; 227:9-15.
cup/disc asymmetry < 0.2 Other 8% 6% 0.15 Control
0.15 NTG 5 Dreyer EB, Zurakowski D, Schumer RA, Podos SM, Lipton SA. Elevated glutamate levels in the vitreous
unremarkable red-free ophthalmoscopic examinations. HTN 41% 44% 0.1 0.1
Control body of humans and monkeys with glaucoma. Arch Ophthalmol 1996; 114:299-305.
0.05 6 Lee HM, Weinstein JN, Meller ST, Hayashi N, Spratt KF, Gebhart GF. The role of steroids and their effects
DM 24% 19%
No family history of glaucoma. 0 0.05 on phospholipase A2 in an animal model of radiculopathy. Spine 1998; 23(11):1191-6.
IOP Max 18.4 0.27 17.3 0.29 P=0.0053 7 Hall ED. Neuroprotective actions of glucocorticoid and nonglucocorticoid steroids in acute neuronal
Maximum IOP less then 21mmHg. indicates p>0.05
0 injury. Cell Mol Neurobiol 1993; 13:415-32.
CE Total 8 Lindsey JD, Weinreb RN. Survival and differentiation of purified retinal ganglion cells in a chemically
Controls did not undergo visual field testing. defined microenvironment. Invest Ophthalmol Vis Sci 1994; 35:3640-8.45