**5. Clinical manifestations and classifications**

NVG could be underestimated in early stages of the disease, because there are very few signs that may be easily missed in a routine ophthalmologic exam. It's very important to identify patients who are at risk of developing NVG, specially those that have PDR or ische‐ mic CRVO.

#### **5.1. Early manifestations of neovascular glaucoma**

INV could be seen like fine vessels at the pupillary margin in early stages, in fact INV starts in most cases at this level (Figure 2). In a small number of patients, neovasculariza‐ tion could start at the angle, making gonioscopy with an undilated pupil mandatory to all patients at risk of NVG. Careful gonioscopy is essential to detect early angle NV and ear‐ ly anterior synechiae. Other early signs often seen in NVG are flare, and sometimes a few cells, which may erroneously be diagnosed as a sign of uveitis.(Will Whitmire, Moham‐ med MH Al-Gayyar, et, al. 2011).

#### **5.2. Late manifestations of neovascular glaucoma**

Late manifestations of NVG appear when the disease is well established and the IOP is ele‐ vated. These include mid-peripheral neovascularization of the iris (Figure 3), neovasculari‐ zation of the trabecular meshwork when the angle is still open, fibrovascular membrane over the iris and angle, peripheral anterior synechiaes, progressive angle closure and ectro‐ pion uvea.

#### **5.3. Fluorescein iris angiogram classification**

**4.4. Physiopathology of optic nerve damage**

340 Glaucoma - Basic and Clinical Aspects

hammed MH Al-Gayyar, et, al. 2011).

mic CRVO.

pion uvea.

VEGF, the main protein in the pathogenesis of NVG, plays a nonvascular and neuropro‐ tective role in adult normal retinas. VEGF-A neutralization can cause neuroretinal cell apoptosis and loss of retinal function without affecting the normal vasculature of the reti‐ na. Treatment with VEGF-B protects retinal ganglion cells (RGC) in various models of neurotoxicity. This neuroprotective effect of VEGF-B was attributed to inhibition of proapoptotic proteins like p53 and caspases. The detrimental effects in environments with ex‐ cessive VEGF-A, as happens in PDR, might be explained by excessive levels of peroxynitrite that can inhibit the VEGF-mediated survival signal via tyrosine nitration and subsequent inhibition of key survival proteins in retinal cells. (Will Whitmire, Mo‐

Ischemia of the optic nerve head is the main reason of optic nerve damage in NVG. As the IOP rises the perfusion pressure decreases, worsening the ischemic condition of the optic

NVG could be underestimated in early stages of the disease, because there are very few signs that may be easily missed in a routine ophthalmologic exam. It's very important to identify patients who are at risk of developing NVG, specially those that have PDR or ische‐

INV could be seen like fine vessels at the pupillary margin in early stages, in fact INV starts in most cases at this level (Figure 2). In a small number of patients, neovasculariza‐ tion could start at the angle, making gonioscopy with an undilated pupil mandatory to all patients at risk of NVG. Careful gonioscopy is essential to detect early angle NV and ear‐ ly anterior synechiae. Other early signs often seen in NVG are flare, and sometimes a few cells, which may erroneously be diagnosed as a sign of uveitis.(Will Whitmire, Moham‐

Late manifestations of NVG appear when the disease is well established and the IOP is ele‐ vated. These include mid-peripheral neovascularization of the iris (Figure 3), neovasculari‐ zation of the trabecular meshwork when the angle is still open, fibrovascular membrane over the iris and angle, peripheral anterior synechiaes, progressive angle closure and ectro‐

nerve and retinal ganglion cells. (Ciro Costagliola, Ugo Cipollone, et, al. 2008).

**5. Clinical manifestations and classifications**

**5.1. Early manifestations of neovascular glaucoma**

**5.2. Late manifestations of neovascular glaucoma**

med MH Al-Gayyar, et, al. 2011).

Fluorescein iris angiogram could help differentiate normal iris vessels from INV. The vascu‐ lar abnormalities revealed by fluorescein angiography of the iris are: dilated leaking vessels around the pupil, irregular or slow filling of the radial arteries, superficial arborizing neo‐ vascularization, usually starting in the angle; and dilatation and leakage of the radial ves‐ sels, particularly the arteries. (Leila Laatikainen, 1979). On the basis of angiographic findings, diabetic iridopathy was divided in 4 grades (Table 4).

**Figure 2.** Early rubeosis at the pupillary margin. Photography from the Glaucoma Service, Asociación Para Evitar la Ce‐ guera en México.

**Figure 3.** Late rubeosis with mid-peripheral neovascularization of the iris. Photography from the Glaucoma Service, Asociación Para Evitar la Ceguera en México.


Walsh JB, 1981). This classification is no longer used in our glaucoma service, because treat‐

Neovascular Glaucoma http://dx.doi.org/0.5772/53115 343

3 Neovascularization of the pupillary zone more than 2 quadrants + ectropion uvea or less than 2

In order to differentiate patients for specific treatments, we classify NVG patients in three stages, depending on the characteristics of the angle, the iris and IOP, since the advent of anti-angiogenics and their rapid onset of action has made the amount of iris neovasculariza‐ tion irrelevant in the absence of angle closure. (Castaneda-Díez, García-Aguirre, 2010.)

2 Clinically evident Iris or angle neovascularization with open angle and IOP between 20 and 30 mmHg. 3 Prominent iris and/or angle neovascularization with angle closure, ectropion uvea and IOP over 30

The management of neovascular glaucoma is summarized in figure 5, and depends on whether the angle is open or closed, and whether media are clear or not in order to correctly

Measures to decrease the amount of VEGF produced by the retina, or its effects: Pan-retinal

Measures to control intraocular pressure: Medications to reduce intraocular pressure and/or

Neovascular glaucoma is best treated with prevention. Since retinal ischemia (and VEGF production) is the main predisposing factor for the development of rubeosis iridis, angle ne‐ ovascularization and NVG, laser photocoagulation to the areas of retinal ischemia continues

4 Ectropion uvea and more than 3 quadrants of neovascularization at the iris ciliary zone

ment has changed with the use of antiangiogenic drugs.

1 Neovascularization of the pupillary zone less than 2 quadrants 2 Neovascularization of the pupillary zone more than 2 quadrants

**Table 5.** Clinical grading system of Iris Neovascularization. (Teich SA, Walsh JB, 1981).

1 Early Iris or angle neovascularization with open angle and normal IOP

**Table 6.** Clinical classification of Neovascular Glaucoma. (Castaneda-Díez, García-Aguirre, 2010.)

**6. Medical and surgical treatment of neovascular glaucoma**

photocoagulation, antiangiogenic drugs and/or pars-plana vitrectomy.

visualize the retina. Management can be divided in:

0 Absence of iris neovascularization

Grade Characteristics

filtering procedures.

**6.1. Pan-retinal photocoagulation**

mmHg.

quadrants at iris ciliary zone

**Grade**

**Table 4.** Classification of rubeosis iridis in diabetic eye disease. (Leila Laatikainen, 1979).

In preproliferative and proliferative DR, iris fluorescein angiogram detection of iris neoves‐ sels has a reported sensitivity of 56% and a specificity of 100%. (Francesco Bandello, Rosario Brancato. 1994).

**Figure 4.** Neovascularization of the trabecular meshwork and anterior peripheral synechiae. Photography from the Glaucoma Service, Asociación Para Evitar la Ceguera en México.

#### **5.4. Clinical classifications**

A clinical grading system was also proposed in order to guide pan-retinal photocoagulation therapy, and to select patients who will respond well to the treatment. (Table 5) (Teich SA, Walsh JB, 1981). This classification is no longer used in our glaucoma service, because treat‐ ment has changed with the use of antiangiogenic drugs.


**Table 5.** Clinical grading system of Iris Neovascularization. (Teich SA, Walsh JB, 1981).

**Grade Findings**

342 Glaucoma - Basic and Clinical Aspects

4 Florid rubeosis

Brancato. 1994).

1 Peripupillary vessel dilatations, Dilated leaking capillaries around the pupil,

Filling of vessels in the early arterial phase and leakage of fluorescein

Prominent arborizing new vessels grown out of the angle, covering a larger iris surface

In preproliferative and proliferative DR, iris fluorescein angiogram detection of iris neoves‐ sels has a reported sensitivity of 56% and a specificity of 100%. (Francesco Bandello, Rosario

**Figure 4.** Neovascularization of the trabecular meshwork and anterior peripheral synechiae. Photography from the

A clinical grading system was also proposed in order to guide pan-retinal photocoagulation therapy, and to select patients who will respond well to the treatment. (Table 5) (Teich SA,

Irregularities in the filling of radial vessels

Filling of new vessels in early arterial phase

New vessels covering the entire iris surface Eversion of the pigmented border of the pupil

**Table 4.** Classification of rubeosis iridis in diabetic eye disease. (Leila Laatikainen, 1979).

2 Early neovascularization of the angle (gonioscopy) Arborizing superficial, early, new vessels

3 Prominent rubeosis with or without NVG

Generalized marked leakage

Complete angle closure

Glaucoma Service, Asociación Para Evitar la Ceguera en México.

**5.4. Clinical classifications**

In order to differentiate patients for specific treatments, we classify NVG patients in three stages, depending on the characteristics of the angle, the iris and IOP, since the advent of anti-angiogenics and their rapid onset of action has made the amount of iris neovasculariza‐ tion irrelevant in the absence of angle closure. (Castaneda-Díez, García-Aguirre, 2010.)


**Table 6.** Clinical classification of Neovascular Glaucoma. (Castaneda-Díez, García-Aguirre, 2010.)
