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Normal tension glaucoma requires oculosystemic approach

NTG progression is theorized to be a result of optic nerve pathology, with contributing factors such as cardiac and pulmonary disease.

by John R. Martinelli, OD, FAAO

This course is jointly sponsored by PCON, The State University of New York State College of Optometry and Vindico Medical Education. It is COPE-approved for 2 continuing education credits.

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Normal tension glaucoma (NTG) can be described as a glaucomatous optic neuropathy occurring with a baseline intraocular pressure (IOP) of < 20 mm Hg at the time of initial diagnosis. However, it can be argued that NTG is not a separate entity but can be considered a primary glaucoma based on current definitions that exclude IOP. Therefore, the term “normal tension glaucoma” can be considered a misnomer that only characterizes a variation of glaucoma in its truest form – a form that produces optic nerve pathology, retinal nerve fiber layer (RNFL) deficits and subsequent loss of visual field.

Regarding ocular hypertension (OHT) associated with the primary glaucomas, pretreatment IOP of > 21 mm Hg has historically been thought of as the leading risk factor in the development of progressive glaucomatous optic neuropathy. OHT is indeed one of many contributing risk factors; however, its importance has been scrutinized in recent years and has also led to a rethinking and redefining of the glaucomatous condition.

Considering the significant incidence and prevalence of the glaucomas occurring within a wide range of baseline IOPs, a paradigm shift in language defining glaucoma omitting the term “intraocular pressure” has been universally accepted. Known multifactorial contributors to etiology and disease progression further de-emphasize the role of initial IOP levels. In addition, glaucomatous visual field defects may or may not be present depending on the severity of associated optic neuropathy.

HRT analysis confirms asymmetric advanced glaucomatous optic cupping in the left eye with significantly reduced mean RNFL thickness, particularly in the inferotemporal and temporal quadrants. The right ONH demonstrates better unique stereometric analyses; however, the global cup shape measure is actually further from normal compared to the left, suggesting impending progression. Images: Martinelli JR

The American Optometric Association describes glaucoma as a chronic progressive disease that most often presents with characteristics of optic nerve, RNFL and visual field loss. Similarly, the American Academy of Ophthalmology (AAO) describes glaucoma as a multifactorial optic nerve neuropathy with a characteristic acquired loss of optic nerve fibers. It is interesting to note that visual field loss is not a required finding according to the AAO definition, but of course visual field loss is the eventual result of progressive disease.

Dynamics of ocular, systemic conditions

It is important to understand the dynamics of associated ocular and systemic conditions that must be maintained to provide a balanced relationship at the level of the optic nerve head (ONH). It is this synergistic environment that promotes and allows for continued integrity, function and vision.

In contrast, vascular, hematologic, metabolic, axonal or mechanical insults affecting the ONH can disrupt this balance, potentially allowing for progressive glaucomatous optic neuropathy to occur. A genetic predisposition may also be present, leading to increased susceptibility for characteristic neuropathy. Increasing age is an additional factor that should be considered.

Watch for ischemic conditions

Commonly, ischemic conditions produced by nonarteritic or arteritic vascular disease are discovered as an underlying feature in the NTG clinical presentation. Carotid obstruction or giant cell arteritis with associated temporal arteritis can often be associated with unilateral or asymmetric cases. In fact, there may not be a clear distinction between ischemic optic neuropathy and NTG under certain clinical conditions.

It is important that untreated or refractory systemic disease propagating NTG be promptly identified and addressed. Due to the high association with vascular disease, proper diagnostic and radiologic testing as well as communication with appropriate specialists is a priority. Normal tension glaucoma managed correctly can not only lead to vision saving outcomes, but in certain circumstances can lead to life saving systemic intervention.

Case report

An 83-year-old Caucasian woman came in for a routine examination on Nov. 29, 2006. Her chief complaint was: “I sometimes have a film over my left eye.” She was uncertain of when her vision had changed. She previously underwent uneventful cataract surgery with posterior chamber IOL placement in both eyes in 2003; otherwise, she had no significant ocular history.

The patient was being treated for hypertension and hypercholesterolemia, which were controlled with Accupril (quinapril HCl, Pfizer) 20 mg daily and Lipitor (atorvastatin, Pfizer) 20 mg daily. She reported having a mother who was diagnosed with glaucoma and cataracts. She revealed no additional ocular or systemic family history.

Best corrected visual acuity with refraction was 20/20 OD and 20/25 OS with no improvement with pinhole. Color plates were normal for each eye. Stereopsis was normal. Confrontation visual fields were full in the right eye; however, there was evidence of a mild inferonasal constriction in the left eye. Pupils were equal, round and responsive to light and accommodation. No afferent pupillary defect was elicited in the left eye.

Extraocular muscle versions were full and unrestricted without subjective diplopia. Biomicroscopic examination revealed a healthy anterior segment with a well placed posterior chamber phacoprosthesis in each eye. Tear break-up time was slightly reduced at 9 seconds in both eyes, indicating a mild evaporative dry eye.

Goldmann applanation tonometry was 16 mm Hg OD and 18 mm Hg OS. Goldmann three-mirror gonioscopy showed a grade IV open angle in all four quadrants of both eyes. All angle structures were viewed in each eye including Schwalbe’s line, trabeculum, Schlemm’s canal, scleral spur and ciliary body. Trace pigment was present within the trabeculum in both eyes, with no evidence of pseudoexfoliative debris in either eye.

The anterior chamber was found to be clear and quiet with no sign of current or previous ocular inflammatory activity in either eye. Dilated 90-D ophthalmoscopic evaluation showed a clear vitreous in each eye; however, a posterior vitreous detachment and Weiss ring was apparent in both eyes. The periphery was normal in each eye.

Early involutional and hypertensive arteriolarsclerotic retinal vascular changes with arteriovenous nicking could be appreciated in both eyes. The macula in each eye showed early dry age-related macular degeneration changes with retinal pigment epithelial hyperplasia and perifoveal drusen.

The optic disc in the right eye was found to be asymmetric showing a smaller disc diameter and less cupping compared to the fellow eye. A cup-to-disc ratio of 0.3/0.3 was viewed in the right eye. The optic disc of the left eye was found to have advanced vertical cupping extending inferiorly with significant thinning of neuroretinal rim tissue in the lower quadrant. A cup-to-disc ratio of 0.5/0.8 was viewed in the left eye. Early optic disc pallor was also present in both eyes.

Preliminary diagnosis of NTG

Based on these findings, a preliminary diagnosis of NTG in both eyes much greater in the left, was suspected. Pachymetry measurements were then obtained and were quite favorable at 664 µm OD and 654 µm OS.

ONH HRT II (Heidelberg Engineering, Vista, Calif.) analysis was also performed, confirming asymmetric advanced glaucomatous optic cupping in the left eye with significantly reduced mean RNFL thickness, particularly in the inferotemporal and temporal quadrants. Interestingly, the right ONH demonstrated better unique stereometric analyses; however, the global cup shape measure was actually further from normal compared to the left, suggesting impending progression.

Digital stereoscopic photographs also showed asymmetric glaucomatous optic neuropathy, greater in the left, with slight optic pallor present in both eyes. A 30-2 threshold visual field was performed, which was full in the right eye but revealed an early characteristic glaucomatous Bjerrum’s scotoma along with a nasal step defect in the left eye. The visual field loss correlated nicely with the ONH HRT and photographic evidence of the left eye.

While taking into account the slight acuity reduction of the left eye, a definitive diagnosis of normal tension glaucoma in both eyes, advanced in the left, with early secondary glaucomatous optic atrophy vs. ischemic optic neuropathy in the left eye was concluded. The reduction in acuity in the left eye could also be attributed to the early dry AMD observed.

Consider systemic contribution

Due to the marked asymmetry in the left eye with mild microvasculopathy and optic pallor present in each eye, an underlying systemic contributor must be ruled out. Considering the patient’s history of hypertension and elevated cholesterol, an ischemic vascular component was first pursued, and a treatment plan outlined in the accompanying chart was recommended.

The patient was advised of the likelihood for additional topical adjunctive therapy as well as the possibility of selective laser trabeculoplasty (SLT) treatment to achieve a proper target pressure. A goal of =12 mm Hg in both eyes was set, equating to a 25% reduction in the right eye and a 33% reduction in the left eye, being an effectual drop for the left eye.

In addition to the laboratory studies, an MRI of the head and orbits was also required to rule out associated ischemic cerebrovascular disease or compressive orbital disease in the left eye. Although the patient reported no history of demyelinating disease, the possibility of previous recurrent optic neuritis in the left eye is also a consideration, perhaps allowing for greater probability of glaucomatous progression in that eye. The MRI results would provide further insight in this regard as well.

The patient was encouraged to follow up with her primary care physician with a report of these findings and to reevaluate her blood pressure, cholesterol levels and cardiovascular and general health.

She was scheduled for a 1-month return visit to reassess visual acuity and IOP and to review laboratory findings.

One-month follow-up visit

The patient returned as scheduled for her 1-month follow-up visit. She had recently seen her primary care physician who reported her general health as being stable with adequate blood pressure and cholesterol control and without detectable cardiovascular disease. The patient stated no changes in her vision and acknowledged compliance with her topical treatment (Travatan, travoprost, Alcon).

Doppler findings were noncontributory, demonstrating 16% to 39% of external and internal carotid stenosis on each side with no evidence of asymmetry. Her blood work returned unremarkable with regard to disseminating inflammatory disease, disorders of coagulation or blood dyscrasia.

Corrected visual acuity remained 20/20 OD and 20/25 OS. Interestingly, her Goldmann applanation IOP increased in the right eye to 19 mm Hg and was unchanged at 18 mm Hg in the left.

Despite the laboratory findings and the primary care physician’s report, the patient’s age, hypertension, hypercholesterolemia, retinal microvasculopathy and presence of optic pallor suggested ischemic conditions. Therefore, in this case, Travatan was continued due to the possibility of improved ocular blood flow rather than IOP efficacy, as reported by Inan and colleagues. Additionally, Azopt (brinzolamide 1%, Alcon) 1 drop every 12 hours in both eyes was added, with the possibility of SLT treatment in both eyes to help attain our target IOP. The patient was scheduled to return in 1 month to reevaluate her visual acuity and IOP.

Two-month follow-up

The patient returned as scheduled after 1 month. She reported no change in her vision and confirmed her compliance with both topical medications.

Corrected visual acuity was stable at 20/20 OD and 20/25 OS. IOP in the right eye was unchanged from the initial baseline at 16 mm Hg but reduced to 15 mm Hg in the left eye, signifying some response to the dual topical treatment.

To help maintain our target IOP, a 40 mw/400 µm 100-spot SLT treatment was applied 360º to the trabeculum in the left eye. As is our protocol to facilitate responsiveness, no additional postoperative topical medications were recommended. She was instructed to continue Travatan and Azopt as prescribed and was scheduled for a 10-day postoperative visit for SLT in the right eye.

Ten-day postoperative visit

The patient returned as scheduled for her 10-day postoperative visit. She continued to be compliant with her topical treatment and was asymptomatic following SLT in the left eye. Her corrected vision remained 20/20 OD and 20/25 OS.

Her IOP on this visit was further decreased to 13 mm Hg OD and 12 mm Hg OS, representing a 19% and 33% drop, respectively, from baseline. With target pressure achieved in the left eye, the right eye received the same 40 mw/400 µm 100-spot SLT treatment applied 360º to the trabeculum. (The patient was amenable to the possibility of stopping the drops in the right eye after undergoing SLT.) As before, no additional postoperative topical medications were recommended, and the patient was asked to return in 10 days.

Postoperative visit for second procedure

The patient returned as scheduled for her 10-day postoperative visit. She was compliant with her topical medications and was asymptomatic following SLT in the right eye. Corrected visual acuity was the same at 20/20 OD and 20/25 OS. IOP was now found to be 11 mm Hg OD and 12 mm Hg OS. The reduction in the right eye now represented a 31% drop from baseline with target pressure successfully achieved in both eyes.

In addition to sustaining the topical therapy, the patient was educated about the importance of scheduled IOP, HRT, photography and visual field testing. She was reminded of her early dry AMD and the relevance to her central acuity. A baseline macular HRT analysis was scheduled for a later date and she was re-instructed on using the Amsler grid at home as well as continuing vitamin therapy with Ocuvite (Bausch & Lomb, Rochester, N.Y.). Finally, an MRI of the head and orbits was once again recommended with an order written to rule out associated ischemic cerebrovascular or orbital disease. The patient had been hesitant to pursue this avenue, although the significance was emphasized with respect to providing a more complete assessment of her condition.

NTG and primary glaucoma

NTG can be considered part of a continuum of the primary glaucomas with respect to current defining criteria omitting the term “intraocular pressure,” according to Drugs and Therapy Perspectives. The presence of glaucomatous optic nerve damage and retinal nerve fiber layer deficits, with or without characteristic visual field defects, is now known to be possible at any IOP. Therefore, an intrinsic predisposition with respect to structure, integrity and susceptibility of the ONH and RNFL must first be present for eventual pathology to develop.

An asymmetric presentation may indicate more advanced systemic, orbital or ocular disease occurring on the same side as the further progressed neuropathy. True for all glaucomas, the presence of glaucomatous optic neuropathy must not be assumed isolated and independent of other conditions. A holistic oculosystemic approach should be maintained with causative factors considered in the therapeutic methodology.

The clinical presentation of NTG may be easily overlooked if the practitioner is relying on IOP as the sole initial diagnostic indicator for glaucoma. In line with current thinking, the clinical relevance of baseline IOP in all patients should be viewed as only one of many diagnostic features when assessing the optic nerve. By definition, it is the study and scrutiny of the optic nerve itself and RNFL integrity that are first and foremost in making proper diagnostic decisions.

Importantly, generalized oculosystemic considerations such as noninflammatory and inflammatory vascular disease, carotid disease, cardiac disease, hematologic disorders, pulmonary disease, metabolic conditions, demyelinating disease, orbital disease, ocular disease, trauma, surgery, age and genetic variants can all play a part in the proper diagnosis, management and prognosis. Therefore, the treatment of these same conditions may be equally vital for neuroprotection of the optic nerve as is ocular hypotensive measures. A thorough understanding of appropriate laboratory and radiologic testing is mandatory along with proper communications with relevant specialists to achieve an individualized management plan.

Unilateral NTG calls for additional prudence

Asymmetric or unilateral cases of NTG should be viewed with additional prudence regarding etiology. The possibilities of ipsilateral orbital compressive disease, carotid stenosis or underlying arteritic or nonarteritic ischemic optic neuropathy with simultaneous optic pallor and cupping are only some of the possible clinical scenarios.

Relevant targeted laboratory and radiologic testing is particularly helpful in these cases; it may lead to uncovering a previously unknown and possibly urgent underlying condition. The patient in the case study exhibited asymmetric neuropathy; therefore, an MRI of the head and orbits (emphasis on the left eye) was requested to rule out compressive orbital disease ischemic cerebrovascular disease, as well as evidence of prior demyelinating disease.

Carotid dopplers concentrating on the left side were obtained to explore the possibility of asymmetric vascular insufficiency. Laboratory blood work was ordered looking for evidence of vascular inflammatory disease, autoimmune disease, disorders of coagulation or blood dyscrasia, as well as metabolic dysfunction. In the absence of MRI results, the case did not expose related factors other than older age with hypertension and hypercholesterolemia. Therefore, the exact etiology and pathophysiology of this particular unilateral presentation is difficult to identify.

Causative factors for glaucomatous optic neuropathy

The epidemiologic understanding of NTG can be quite complex considering the many multifactorial associations. Some established causative factors for developing glaucomatous optic neuropathy in normal tension glaucoma are: relatively increased IOP, older age, non-dippers (0 to 10%) or extreme dippers (greater than 20%) when considering nocturnal arterial blood pressure drops, small vessel disease with cardiovascular disease and cerebral microgliosis (white matter lesions), decreased blood flow in the optic nerve head, extreme dip of the optic nerve head blood flow in the morning, cerebral blood flow dysregulation and the epsilon4-allele polymorphism of the apolipoprotein E-gene, according to Baleanu and Michelson.

Concerning pachymetry, glaucoma patients with a thin central corneal thickness are also more likely to be among those diagnosed with NTG, and the underestimation of IOP by Goldmann applanation tonometry may possibly be another diagnostic factor, according to Kniestedt et al.

Regarding poor oxygen profusion to the ONH, Sergi and colleagues found that the prevalence of NTG in obstructive sleep apnea syndrome (OSAS) patients is higher than expected in a white population of the same age, thereby implicating OSAS as a possible important risk factor in NTG as well.

Additionally, Zeyen and the Belgian Glaucoma Society showed that the prevalence of vascular risk factors (VRF) is significantly higher in patients with NTG compared to patients with OHT and glaucoma and that VRF may increase the risk for progression of glaucomatous visual field defects. In this study, visual field progression was found in 34% of the patients with primary open angle glaucoma (POAG) and indeed found to be significantly higher in 46% of the patients with NTG, with both groups exhibiting VRF.

It is therefore not surprising that a related change in microcirculation of the optic nerve head may be more related to visual field damage in NTG patients but may be less involved in visual field damage in POAG patients, according to Yaoeda and colleagues.

Regarding functional vs. anatomic outcome variables, Choi and colleagues found circadian fluctuation of mean ocular profusion pressure to be the most consistent clinical risk factor for glaucoma severity in eyes with NTG. This finding may also suggest an etiology of NTG as a chronic ischemic end organ disease.

As exemplified in the case report, inferior quadrant rim tissue involvement was found to be producing a corresponding superior visual field defect. Sato and colleagues showed inferior rim blood flow in NTG to be less than superior rim blood flow in patients producing superior hemifield defects, and superior rim blood flow is reduced compared to inferior in patients with inferior hemifield defects. Mean superior/inferior ratios of mean blood flow in patients with superior hemifield defects were significantly higher than in patients with inferior hemifield defects. Thus, the blood flow in the neuroretinal rim was found to correspond to regional visual field defects in eyes with NTG.

The 30-2 threshold visual field was full in the right eye but revealed an early characteristic glaucomatous Bjerrum’s scotoma along with a nasal step defect in the left eye. The visual field loss correlated nicely with the ONH HRT and photographic evidence in the left eye. Images: Martinelli JR

This reduction in flow leading to functional and visual field loss was found to be particularly prevalent with cases of inferior rim deficits producing superior visual field defects. Perhaps there may be also some correlation with gravitational effects producing an inferior “collapse” of the optic nerve and retinal ganglion cells under certain clinical conditions. For these reasons, the inferior rim margin of the ONH must be carefully examined when evaluating the potential NTG patient.

Treatment goal

The goal of treatment in the NTG patient is the preservation of optic nerve and RNFL function by inhibiting the progression of glaucomatous optic neuropathy that will ultimately lead to vision loss. Of course, it is accepted that a reduction of IOP is advantageous and will improve the prognosis in glaucoma patients. However, in addition to IOP, the understanding of ocular and systemic conditions specifically influencing ONH hemodynamics has been found to be most valuable.

Toda and Nakanishi-Toda, Galambos and colleagues, Gupta, Huber and colleagues, Harris and colleagues, Weigert and colleagues and Akcar and colleagues have shown the importance of ONH hemodynamics and the need for the development of innovative therapeutic technologies. This knowledge provides the opportunity to recommend supplementary treatment strategies targeting glaucomatous neuropathy from the “back side” rather than purely from an IOP perspective.

Calcium-channel blockers promising treatment

Regarding management of the many possible contributing ocular and systemic conditions discussed previously, calcium-channel blockers seem to be the most promising adjunctive treatment to be considered in patients with glaucomatous optic neuropathy without increased IOP, according to Orgul and colleagues. Calcium-channel blockers are a class of drugs that block the entry of calcium into muscle cells, including those of arterioles found within the ONH. It is the entry of calcium into these cells that causes the muscle to contract and arterioles to narrow. By blocking the entry of calcium, calcium-channel blockers will decrease arteriole contraction, allowing for increased profusion to the optic nerve head, thereby enhancing neuroprotection.

Luksch and colleagues have specifically found the calcium-channel blocker nimodipine to increase ONH and choroidal blood flow in NTG patients. In those with additional vasospastic signs, retinal capillary blood flow is further reduced in comparison with healthy controls, suggesting the need for this treatment modality.

Michalk and colleagues showed single-dose nimodipine to normalize retinal circulation in NTG patients up to values of healthy controls 90 minutes after drug administration.

Hypertension and hypercholesterolemia

As in the case discussed with NTG and hypertension coexisting, common pathogenetic mechanisms in ciliary and renal tubular epithelia may explain a concurrence of glaucoma and systemic hypertension, according to Langman and colleagues. Therefore, the choice of hypertensive and cardiovascular treatments could substantially influence glaucoma incidence, with beta blockade protecting and ACE inhibitors or calcium-channel blockers affecting underlying risk.

Hypercholesterolemia and its treatment with the statin drugs lovastatin and compactin have been found to also induce changes in cell shape and actin cytoskeletal organization along with other biochemical modifications, all of which are events that are likely to lead to cellular and tissue relaxation, according to Song and colleagues. Conceivably, this form of cellular reorganization may lead to another level of neuroprotection for the glaucomatous ONH.

Digital stereoscopic photographs of our patient showed asymmetric glaucomatous optic neuropathy in both eyes, greater in the left, with slight optic pallor present in both eyes. Images: Martinelli JR

Another important finding of Song and colleagues is that statins exert an ocular hypotensive response in an organ-culture perfusion model, indicating additional potential for this class of drugs in glaucoma therapy. Concurrently, the long-term use of oral statins may be associated with a reduced risk of open-angle glaucoma, particularly among those with cardiovascular and lipid diseases, according to McGwin and colleagues. Nonstatin cholesterol-lowering agents were also associated with a reduced risk of having open-angle glaucoma. Additional investigation is warranted as to whether these classes of agents may truly provide another therapeutic option for glaucoma, they said.

Neuroprotection

Pharmacological direct neuroprotection is another active area being researched, which, in the context of glaucoma, refers to the situation in which a drug is deployed to interact with neuronal or glial elements within the optic nerve head/retina, thereby facilitating the survival of retinal ganglion cells (RGC), according to Chidlow and colleagues. Specific cellular targets have been manipulated with varying degrees of success in relevant animal models including glutamate receptors, autoimmune elements, neurotrophin deprivation, nitric oxide synthesis, oxidative stress products, sodium and calcium channels, heat shock proteins and apoptotic pathways.

RGC protection has also been discovered utilizing estrogen hormone therapy, which demonstrated a reduction in loss of RGC and neurofibers through the inhibition of ganglion cell apoptosis, according to Zhou and colleagues. Moreover, estrogen therapy yielded a multitude of various positive biochemical cellular events. This may be yet another example of a future treatment modality.

CHF, COPD

Regarding other risk factors and treatment, glaucoma, particularly NTG, has been associated with both high and low blood pressure variations and stroke, according to Belzunce and Casellas. Respiratory disease such as pneumonia and circulatory disorders such as congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are frequently an underlying causative factor in glaucoma and NTG patients as well. Treatment of these conditions will allow for increased vascular and oxygen profusion to the ONH, aiding in the prevention of progressive glaucomatous optic neuropathy.

It must be noted that one of the most frequent topical therapies used for glaucoma are the beta-blockers, which are contraindicated in COPD and CHF patients. Alternatively, the use of the prostaglandin analogs can not only more safely lower IOP, they have been associated with increased ONH pulsatile blood flow, which is of most concern in these cases, say Baleanu and Michelson.

Finally, Harvey and colleagues have researched gene therapy focusing on RGC regeneration with hopes of leading to new and novel therapies.

Not a simple definition

As evident by the case discussion as well as the examples given of various multifactorial systemic and ocular contributors, NTG cannot be simply defined. The concerns with etiology, pathogenesis and pathophysiology of glaucomatous optic neuropathy in NTG need to be addressed as in ocular hypertensive states. Glaucomatous optic neuropathy can be viewed as the inability of the optic nerve or retinal nerve fiber layer to maintain integrity and function at any pressure, thereby leading to cupping, excavation, loss of neuroretinal rim tissue and eventually loss of vision.

Interestingly, however, results of the Collaborative Normal Tension Glaucoma Study (CNTGS) suggest patients with “true” NTG – without known contributory systemic factors – be first monitored for progression or stability before actually initiating treatment. CNTGS demonstrated that most NTG patients progress slowly or perhaps not at all. (In the case report, we chose to move swiftly with therapy due to her atypical advanced unilateral presentation.) In the case of progression or with additional risk factors, targeting a 30% reduction from baseline IOP is recognized as efficacious.

True for all glaucoma and particularly NTG, developing a treatment plan based primarily on oculosystemic considerations is a most effective way to provide protection of the optic nerve leading to preservation of vision. IOP must be addressed, but only as one part of a bigger picture in the glaucomatous process.

For more information:

• John R. Martinelli, OD, FAAO, is a private practitioner based in Charleroi, Pa. He can be reached at Martinelli Eye and Laser Centers, 303 First Street, Charleroi, PA 15022; (724) 483-3675; fax: (724) 483-0404; e-mail: jrm@martinellieyecare.com; Web site: www.martinellieyecare.com. Dr. Martinelli has lectured for Alcon, AMO and Allergan.

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