**2. Etiology**

There are many systemic disease and ocular conditions that cause neovascular glaucoma, but they all share a common etiology, which is retinal ischemia, and hypoxia that triggers a

© 2013 Esponda-Lammoglia et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

pro-angiogenic cascade that finally causes the growth of defective vessels with altered per‐ meability. There are three common causes of NVG: Proliferative diabetic retinopathy, cen‐ tral retinal vein occlusion and ocular ischemic syndrome.

*2.1.3. Ocular ischemic syndrome*

**2.2. Uncommon causes**

*2.2.1. Ocular tumors*

*2.2.2. Uveitis*

angle and retina.

Diabetes mellitus\*

Sickle cell disease\*

Takayasu's disease

Retinal detachment

Coats' disease Tumors

Eales' disease Multiple sclerosis

Age-related macular degeneration\*

Retinopathy of prematurity\*

Systemic lupus erythematosus

Distal large artery occlusion

Carotid artery obstruction

**Diseases Associated With Retinal Neovascularization**

Central retinal vein occlusion\* Branch retinal vein occlusion\*

\*Most frequently associated with retinal neovascularization

**Table 1.** Diseases associated with retinal neovascularization

Ocular ischemic syndrome is caused by reduced blood flow to the eye, which produces anterior and posterior segment ischemia, resulting in the development of iris and angle neovasculariza‐ tion. This is caused by severe carotid artery occlusion (greater than 90%), occlusive disease of the aortic arch or the ophthalmic artery, and less frequently when the ciliary arteries are involved.

Neovascular Glaucoma http://dx.doi.org/0.5772/53115 335

The development of NVG has been reported in several ocular tumors such as melanoma, choroi‐ dal hemangioma, retinoblastoma, malignant lymphoma and some metastatic tumors. Radia‐ tion retinopathy after the treatment of certain tumors has been associated with the development

NVG has been reported in both anterior and posterior uveitis. It is thought that inflamma‐ tion and its related Inflammatory factors may directly cause neovascularization on the iris,

of NVG because irradiation causes retinal capillary non-perfusion and retinal ischemia.

#### **2.1. Common causes**

### *2.1.1. Proliferative diabetic retinopathy*

Neovascular Glaucoma is a late manifestation of proliferative diabetic retinopathy (PDR), al‐ though it may occur due to ischemia, before neovascularization of the retina or optic disc are present, the most common presentation is in association with PDR. The time of progression from iris neovascularization (IN) to neovascular glaucoma (NVG) is not well established be‐ cause in some cases it progresses very rapidly, in others it might remain stable for years or even regress with treatment.

The reported rate of IN is 1-10% among all diabetics and about 64% among patients with PDR. Prevalence of NVG in DM is 2%, but it increases to 21% in PDR where the frequency of IN can be as high as 65%. All of these risk factors plus activation of the inflammation cas‐ cade by ocular surgery makes the incidence of NVG, rise to 80%, in eyes after pars plana vitrectomy.

NVG is caused more frequently by diabetes than by retinal vein occlusions in Mexico. The proportion is precisely the opposite as that reported in a classic work (Brown et al. 1984). We found that 114 out of 134 (85%) patients operated with an Ahmed valve for NVG during a 22-month period were diabetic (Albis-Donado et al. 2012).

#### *2.1.2. Central retinal vein occlusion*

One third of the central retinal vein occlusion (CRVO) cases are ischemic at presentation, the remaining two thirds are non-ischemic, but with a conversion to ischemic rate of about 10%. NVG is a frequent complication of ischemic central retinal vein occlusion. The larger the area of capillary non-perfusion, the greater the risk of developing NVG, especially during the first 18 months.

In general, the development of NVG in CRVO depends upon the severity and extent of the ischemia, for example, hemi retinal vein occlusion or branch retinal vein occlusion have a lower risk of developing NVG and in either case, only if ischemic. Studies have indicated that at least half of the retina must be ischemic for NVG to develop.

In cases in which the ischemic subtype was not defined, the incidence of NVG at 6 months after the CRVO was 50%. In cases of non-ischemic CRVO, the incidence of NVG was ap‐ proximately 1% eight to fifteen months after the event. NVG incidence in ischemic CRVO ranged from 23% to 60%, but it has been reported to be as high as 80% over a period of 12 to 15 months.

#### *2.1.3. Ocular ischemic syndrome*

Ocular ischemic syndrome is caused by reduced blood flow to the eye, which produces anterior and posterior segment ischemia, resulting in the development of iris and angle neovasculariza‐ tion. This is caused by severe carotid artery occlusion (greater than 90%), occlusive disease of the aortic arch or the ophthalmic artery, and less frequently when the ciliary arteries are involved.

#### **2.2. Uncommon causes**

#### *2.2.1. Ocular tumors*

pro-angiogenic cascade that finally causes the growth of defective vessels with altered per‐ meability. There are three common causes of NVG: Proliferative diabetic retinopathy, cen‐

Neovascular Glaucoma is a late manifestation of proliferative diabetic retinopathy (PDR), al‐ though it may occur due to ischemia, before neovascularization of the retina or optic disc are present, the most common presentation is in association with PDR. The time of progression from iris neovascularization (IN) to neovascular glaucoma (NVG) is not well established be‐ cause in some cases it progresses very rapidly, in others it might remain stable for years or

The reported rate of IN is 1-10% among all diabetics and about 64% among patients with PDR. Prevalence of NVG in DM is 2%, but it increases to 21% in PDR where the frequency of IN can be as high as 65%. All of these risk factors plus activation of the inflammation cas‐ cade by ocular surgery makes the incidence of NVG, rise to 80%, in eyes after pars plana

NVG is caused more frequently by diabetes than by retinal vein occlusions in Mexico. The proportion is precisely the opposite as that reported in a classic work (Brown et al. 1984). We found that 114 out of 134 (85%) patients operated with an Ahmed valve for NVG during a

One third of the central retinal vein occlusion (CRVO) cases are ischemic at presentation, the remaining two thirds are non-ischemic, but with a conversion to ischemic rate of about 10%. NVG is a frequent complication of ischemic central retinal vein occlusion. The larger the area of capillary non-perfusion, the greater the risk of developing NVG, especially during

In general, the development of NVG in CRVO depends upon the severity and extent of the ischemia, for example, hemi retinal vein occlusion or branch retinal vein occlusion have a lower risk of developing NVG and in either case, only if ischemic. Studies have indicated

In cases in which the ischemic subtype was not defined, the incidence of NVG at 6 months after the CRVO was 50%. In cases of non-ischemic CRVO, the incidence of NVG was ap‐ proximately 1% eight to fifteen months after the event. NVG incidence in ischemic CRVO ranged from 23% to 60%, but it has been reported to be as high as 80% over a period of 12 to

tral retinal vein occlusion and ocular ischemic syndrome.

22-month period were diabetic (Albis-Donado et al. 2012).

that at least half of the retina must be ischemic for NVG to develop.

**2.1. Common causes**

334 Glaucoma - Basic and Clinical Aspects

*2.1.1. Proliferative diabetic retinopathy*

even regress with treatment.

*2.1.2. Central retinal vein occlusion*

the first 18 months.

15 months.

vitrectomy.

The development of NVG has been reported in several ocular tumors such as melanoma, choroi‐ dal hemangioma, retinoblastoma, malignant lymphoma and some metastatic tumors. Radia‐ tion retinopathy after the treatment of certain tumors has been associated with the development of NVG because irradiation causes retinal capillary non-perfusion and retinal ischemia.

#### *2.2.2. Uveitis*

NVG has been reported in both anterior and posterior uveitis. It is thought that inflamma‐ tion and its related Inflammatory factors may directly cause neovascularization on the iris, angle and retina.


**Table 1.** Diseases associated with retinal neovascularization


and other conditions such as ocular ischemic syndrome and tumors. Approximately 36% of NVG occurs after CRVO, 32% with PDR, and 13% occurs after carotid artery obstruction. Given that the underlying etiology of developing NVG is some form of retinal ischemia, it is more prevalent in elderly patients who have cardiovascular risk factors such as hyperten‐ sion and diabetes, and may be more aggressive in those with obstructive sleep apnea syn‐

Neovascular Glaucoma http://dx.doi.org/0.5772/53115 337

Salus first observed abnormal vessels in the iris in 1928, calling the condition rubeosis iridis. Neovascularization of the iris (INV) is often followed by NVG, with its associated blindness and pain. (Laatikainen, 1979). The most common conditions that develop NVG as a compli‐ cation of the disease are Diabetic Retinopathy (DR) and Central Retinal Vein Occlusion (CRVO), both having retinal hypoxia and ischemia as main contributory factor. (Al-Shamsi

Retinal hypoxia-ischemia increases the production of multiple factors: Vascular endothelial grow factor, nitric oxide, inflammatory cytokines, free radicals and accumulation of intracel‐ lular glutamate. (Charanjit Kaur et, al. 2008). The mechanism for reaching the critical level of retinal hypoxia-ischemia is different between DR and CRVO, because the first may need years to reach the level of VEGF that can develop INV and NVG, but CRVO could reach that

Green made the most relevant histopathology study, in our opinion, in 1981. This study showed the natural history and characteristic evolution of thrombi in CRVO. First there is

Inflammatory cell infiltration becomes prominent as a secondary factor. In early thrombosis, neutrophils may be seen clinging to the wall of the vein. After several weeks, a variable de‐ gree of lymphocyte infiltration was present in almost half of their cases. The infiltrate was seen in three places: around the vein (periphlebitis), in the wall of the vein (phlebitis) and/or in the occluded area. Endothelial-cell proliferation is an integral part of the process of organ‐

In some of the eyes with an interval of a year or more between CRVO and the histologic study, a thick-walled vein with a single channel was present. They believe that these cases represent an old thrombus that now has a single or a main channel of recanalization. (Green,

Rubeosis iridis and NVG had a high prevalence in Green's study, reaching 82.8%. Other au‐ thors had previously described the high incidence of rubeosis iridis in CRVO, associated with clinical risk factors such as visual acuity less than 6/60 (20/200), more than 10 cottonwool spots and/or severe retinal oedema seen by ophthalmoscopy. Some fluorescein angiog‐

adherence of the thrombus to an area of the vein wall without its endothelium.

ization and recanalization of the thrombus, and it occurs after several days.

drome (Shiba et al. 2009 and Shiba et al. 2011).

**4. Physiopathology**

HN, Dueker DK, et, al. 2009)

level in only a few weeks.

et al.1981)

**4.1. Physiopathology of central retinal vein occlusion**

#### **Diseases Associated With Iris Neovascularization**

**Table 2.** Diseases Associated With Iris Neovascularization

### **3. Prevalence and incidence**

Overall incidence and prevalence of NVG has not been accurately reported, a retrospective study has shown a prevalence rate of 3.9%. The most common conditions associated with NVG are central retinal vein occlusion (CRVO), proliferative diabetic retinopathy (PDR), and other conditions such as ocular ischemic syndrome and tumors. Approximately 36% of NVG occurs after CRVO, 32% with PDR, and 13% occurs after carotid artery obstruction. Given that the underlying etiology of developing NVG is some form of retinal ischemia, it is more prevalent in elderly patients who have cardiovascular risk factors such as hyperten‐ sion and diabetes, and may be more aggressive in those with obstructive sleep apnea syn‐ drome (Shiba et al. 2009 and Shiba et al. 2011).
