Expanding horizons of intravitreal anti-vascular endothelial growth factor therapy in retinal diseases

Abstract

Vascular endothelial growth factor (VEGF) plays a central role in the pathogenesis of retinal and choroidal neovascularization, as well as macular edema (ME), in retinal disorders such as diabetic retinopathy, retinal vein occlusion (RVO), and age-related macular degeneration (ARMD). The advent of intravitreal anti-VEGF therapy has revolutionized their management. More recently, these agents have been explored in several other retinal pathologies characterized by secondary neovascularization, either in vascular or non-vascular disorders. This review summarizes current evidence on the role of anti-VEGF agents in retinal disorders other than ARMD, including central serous chorioretinopathy (CSCR), macular telangiectasia type 2 (MacTel), choroidal osteoma, retinopathy of prematurity (ROP), tubercular granuloma, inherited retinal dystrophies, Coats’ disease, angioid streaks, and retinal vasoproliferative tumors (RVPTs).

Methods of literature search

The authors conducted a search of the PubMed, Google Scholar, and Cochrane databases using the following terminologies: vascular endothelial growth factor (VEGF); intravitreal anti-VEGF; central serous chorioretinopathy; macular telangiectasia; Coats’ disease; angioid streaks; choroidal osteoma, vasoproliferative tumors, retinopathy of prematurity (ROP), choroidal tuberculoma, inherited retinal disease (IRD). For articles not published in English or without translations, only English abstracts were used.

VEGF causes retinal and choroidal neovascularization and macular edema (ME) in common retinal disorders such as age-related macular degeneration (ARMD), polypoidal choroidal vasculopathy (PCV), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). Intravitreal anti-VEGF therapy has transformed the management of these conditions, providing significant visual improvement and anatomical stabilization for many patients. Beyond these established indications, the anti-angiogenic and anti-vasculogenic effects of VEGF inhibition have prompted investigation into its use across a range of other retinal disorders. These less common yet clinically significant entities often involve either vascular leakage or secondary neovascularization.[1] Pro re nata (PRN) regimen of anti-VEGF therapy has proven to be beneficial either as adjunctive therapy with established modes of treatment like photodynamic therapy (PDT), cryotherapy in retinal vascular disorders, and as anti-vasculogenic therapy in diseases like aggressive retinopathy of prematurity (A-ROP).[2] Anti-VEGFs have also proven beneficial in treating secondary choroidal neovascularization in diseases like choroidal osteomas as well as inherited retinal disorders complicated by choroidal neovascularization, like retinitis pigmentosa (RP), best disease, etc., Certain vascular retinal tumors like capillary hemangiomas and vasculoproliferative tumors respond well to anti-VEGF therapy with reduction in subretinal fluid (SRF) accumulation and tumor regression. The predictable pharmacokinetics and known intravitreal half-life of anti-VEGF agents, availability of high-resolution imaging modalities (optical coherence tomography [OCT], OCTA) enabling objective and reproducible assessment of anatomical response, has been key facilitators for expanding therapeutic indications of anti-VEGF agents. This review consolidates current literature and clinical experience on the expanding role of anti-VEGF agents in a myriad of vascular and non-vascular retinal diseases, highlighting therapeutic outcomes, limitations, and safety considerations.

Vascular Disorders

A) Macular Telangiectasia Type 2 (MacTel 2)

Macular telangiectasia type 2 (MacTel 2) is a bilateral, asymmetric, progressive neuro-vascular maculopathy characterized by parafoveal telangiectatic vessels and intraretinal hyporeflective cavities on OCT. Fluorescein angiography (FA) typically reveals deep intraretinal leakage temporal to the fovea without significant thickening of the macula.[3,4] Clinically, the disorder is classified as non-proliferative when telangiectasia and foveal atrophy predominate, and as proliferative when MNV develops. Anti-VEGF agents are mainly indicated in the proliferative stage to treat secondary MNV and stabilize or improve visual acuity.[5] Patients with proliferative MacTel 2 show more significant improvement in best-corrected visual acuity (BCVA) than those with non-proliferative disease.[6] By blocking VEGF-induced vascular permeability and neovascular complex formation, intravitreal anti-VEGF therapy decreases ME and improves or maintains central vision.[7]

Çoban Karataş et al.[8] demonstrated that patients with proliferative MacTel 2 and declining visual function benefit from anti-VEGF therapy. Karasu and Gunay[9] compared different anti-VEGF agents: aflibercept, ranibizumab, and bevacizumab, and found all to be effective in achieving favorable anatomical and visual outcomes in proliferative disease. In contrast, Charbel Issa et al.[10] reported no functional benefit of monthly ranibizumab in the non-proliferative stage despite transient anatomical effects, concluding that routine treatment is not warranted in this phase. Similarly, Aydoğan et al.[11] observed that anti-VEGF therapy produced anatomical improvement only with continued injections, reinforcing the need for long-term monitoring. Overall, anti-VEGF agents appear to stabilize vascular leakage and macular thickness in proliferative MacTel 2, whereas evidence for benefit in non-proliferative disease remains inconclusive.[12,13] Anti-VEGF therapy represents the current standard of care for proliferative MacTel 2 associated with macular neovascularization (MNV), offering both anatomical and visual gains. However, its use in the non-proliferative stage provides only transient anatomical improvement without sustained visual benefit. Further controlled studies are required to define optimal treatment intervals and long-term outcomes.

B) Coats’ Disease

Coats’ disease is an idiopathic retinal vascular disorder characterized by telangiectatic and aneurysmal vessels associated with intraretinal or subretinal exudation, often progressing to exudative retinal detachment [Fig. 1]. The underlying pathology involves disruption of the blood–retinal barrier, leading to abnormal vascular permeability and lipid-rich exudation. Conventional management includes cryotherapy and laser photocoagulation, which target telangiectatic vessels to reduce exudation and prevent progression. However, elevated intraocular levels of VEGF and other inflammatory mediators have been documented in eyes with Coats’ disease, implicating VEGF in disease activity.[14,15] Anti-VEGF agents help restore the integrity of the blood–retinal barrier, reduce vascular leakage, and facilitate the application of focal laser or cryotherapy.[16,17,18] Li et al.[19] reported visual improvement in 41.8% of patients with stage 3B Coats’ disease when intravitreal ranibizumab was combined with cryotherapy and laser photocoagulation. Similarly, several studies have shown that anti-VEGF therapy decreases subretinal exudation, ME, and the number of telangiectatic vessels, resulting in improved anatomical and functional outcomes.[20,21] Yang et al.[22] demonstrated that anti-VEGF combined with laser therapy for early disease or with minimally invasive vitrectomy for advanced stages yields favorable outcomes. However, potential complications have been reported. Ramasubramanian and Shields[23] observed vitreoretinal fibrosis and tractional retinal detachment following bevacizumab therapy in some patients, highlighting the need for cautious use, especially in advanced stages. Anti-VEGF therapy serves as a valuable adjunct in the management of Coats’ disease by reducing exudation and enhancing the efficacy of laser or cryotherapy. Combination treatment offers superior anatomical outcomes compared to monotherapy. However, the potential risk of fibrosis and tractional retinal detachment necessitates careful case selection and close follow-up.

Figure 1.

(a) Color fundus photo of right eye showing exudative lesion with telangiectatic vessels involving the macula at presentation. (b) Infrared reflectance image of the right eye showing the area through which the scan is taken at presentation. (c) Structural OCT image of the right eye showing subfoveal exudates with parafoveal intraretinal cysts at presentation. (d) Color fundus photo of right eye showing decreased exudation after anti-VEGF injection. (e) Infrared reflectance image of the right eye showing the area through which the scan is taken after anti-VEGF injection. (f) Structural OCT image of the right eye showing decreased subfoveal exudation with resolution of parafoveal intraretinal cysts after anti-VEGF injection. OCT = Optical coherence tomography, VEGF = Vascular endothelial growth factor

C) Retinal Capillary Haemangioma (RCH)

Retinal capillary hemangioma (RCH) is a benign vascular tumor that may occur sporadically or as part of von Hippel–Lindau (VHL) disease, an autosomal dominant condition associated with a germline mutation on chromosome 3p26. Sporadic RCHs are typically unilateral and solitary, whereas those associated with VHL are often multifocal and bilateral, occurring in up to 50% of affected individuals. Clinically, RCH presents as a round, orange-red lesion with prominent feeder and draining vessels. Although often asymptomatic in early stages, vision loss can result from exudation involving the macula, vitreous hemorrhage, or tractional changes secondary to glial proliferation. Management options depend on tumor size and location and include observation, cryotherapy, laser photocoagulation, PDT, anti-VEGF therapy, or vitreoretinal surgery.[24,25] Anti-VEGF agents reduce vascular permeability by stabilizing endothelial tight junctions and can be used alone or in combination with PDT, cryotherapy, or laser treatment. Ziemssen et al.[26] described successful regression of juxtapapillary RCH following a single session of combined intravitreal bevacizumab and PDT. Ach et al. and Mennel et al. similarly reported anatomical and visual improvement using combination therapy with bevacizumab, laser, or PDT for juxtafoveal and mid-peripheral lesions.[27,28] Other studies, including those by Ucan Gunduz et al. and Slim et al., demonstrated that adjunctive anti-VEGF therapy may shrink tumor size, reduce vascularity on OCT angiography, and minimize intraoperative bleeding when used before vitreoretinal surgery.[29,30] However, Rogers et al.[31] found that although bevacizumab temporarily reduced tumor thickness in some patients, most required additional treatment for complete regression, indicating only a limited and short-term effect. Thus, while anti-VEGF therapy can enhance anatomical outcomes and facilitate surgical or focal treatment, monotherapy is rarely sufficient for long-term control. Anti-VEGF therapy serves as an effective adjunct in the multimodal management of RCH, improving anatomical stability and facilitating adjunctive laser or surgical treatment. Combination approaches yield superior outcomes compared to monotherapy. However, the temporary nature of the response warrants close follow-up and integrated multimodal therapy in complex or VHL-associated cases.

D) Retinal Vasoproliferative Tumors

Retinal vasoproliferative tumors (RVPTs) are benign vascular tumors that arise within the sensory retina and are most often located in the inferotemporal periphery. They can occur as primary lesions or secondary to other ocular conditions, such as RP, chronic uveitis, Coats’ disease, or longstanding retinal detachment. Clinically, these tumors present as yellow-pink nodular masses that may lead to exudation, SRF accumulation, macular edema, or secondary epiretinal membrane formation. They typically occur in the fourth or fifth decade of life and affect males and females equally.[32] Management options vary according to tumor size and associated complications and include observation, cryotherapy, laser photocoagulation, PDT, brachytherapy, and intravitreal therapy with anti-VEGF agents or steroid implants. VEGF expression has been demonstrated in various retinal vascular tumors, including hemangioblastomas associated with VHL and astrocytic hamartomas, providing a rationale for anti-VEGF therapy.[33] Kenawy et al.[34] successfully treated a patient with RVPT using intravitreal bevacizumab, resulting in a reduction in tumor size and improved visual acuity. Similarly, Chu et al.[35] reported regression of RVPT and absorption of SRF following intravitreal aflibercept injection. However, Rogers et al.[31] observed that in a small series of six patients, bevacizumab monotherapy led to only temporary tumor shrinkage in half of the cases, with most requiring additional intervention for definitive regression. This suggests that anti-VEGF agents may offer short-term benefits in reducing exudation and edema but are seldom curative when used alone. Combination therapy, integrating anti-VEGF agents with cryotherapy, PDT, or laser photocoagulation, has shown improved anatomical outcomes, reduced intraoperative bleeding, and enhanced visual stability. Anti-VEGF therapy offers valuable adjunctive benefits in managing RVPT by reducing exudation, stabilizing vision, and facilitating other focal treatments. However, its effect on tumor regression is often transient, and combined treatment remains the most effective approach for long-term control.

E) Retinopathy of Prematurity

ROP is a vasoproliferative disorder affecting the retina of premature infants and occurring within a few weeks of birth.[36] Based on evidence from the CRYO-ROP and ETROP studies, ablation of the avascular retina with cryotherapy or laser photocoagulation is an established and effective treatment for ROP.[37,38] The role of VEGF in the pathogenesis of ROP has been extensively studied, with retinal neovascularization shown to be primarily VEGF driven.[39] The pathogenesis of ROP is classically divided into two phases: An initial vaso-obliterative phase followed by a vasoproliferative phase. Differential VEGF expression across these phases has important implications for the timing of ROP management.[40,41] Anti-VEGF therapy has emerged as a first-line treatment for zone I ROP and A-ROP, owing to its ability to induce rapid regression of retinal neovascularization while allowing continued physiologic vascularization of the peripheral retina.[42] Among anti-VEGF agents used for ROP, bevacizumab, ranibizumab, and aflibercept are most commonly reported. Ranibizumab is approved for use in the European Union, and aflibercept has recently received approval from the US Food and Drug Administration.[43] Anti-VEGF therapy has been used in the following clinical settings: (1) monotherapy for type 1 ROP (zone I disease with plus at any stage, zone I stage 3 without plus, and zone II stage 2 or 3 with plus); (2) aggressive ROP; (3) salvage therapy following failure of laser photocoagulation; and (4) as an adjunct before surgical intervention for stage 4 or 5 ROP.[2] In the published literature, intravitreal bevacizumab (0.625 mg/0.025 mL) and ranibizumab (0.25 mg/0.025 mL) at half the adult dose are most commonly reported for this procedure.[42,44] Study by Chen et al.[45] reported comparable rates of regression and recurrence with bevacizumab and ranibizumab when used as primary therapy for type 1 ROP. However, case series have reported that a lower dose of bevacizumab (0.375 mg) is effective in inducing regression of retinal neovascularization in ROP.[46]

Non-vascular Disorders

A) Central Serous Chorioretinopathy (CSCR)

Central serous chorioretinopathy (CSCR) is characterized by a serous detachment of the neurosensory retina over an area of leakage from the choriocapillaris through a defect in the retinal pigment epithelium (RPE).[47] Although often a self-limiting condition, chronic CSCR can result in cystoid macular edema (CME) and MNV.[48] The pathophysiology primarily involves choroidal circulatory dysfunction and RPE barrier breakdown, leading to SRF accumulation at the posterior pole. The principal treatment objectives in CSCR are to halt disease progression and enhance SRF absorption. Anti-VEGF agents reduce the permeability and proliferative activity of choroidal endothelial cells by upregulating tight junction integrity and reducing vascular fenestration.[49] These agents are particularly beneficial in CSCR complicated by secondary MNV.[50] Kim et al.[51] reported that in a cohort of 20 patients with chronic CSCR, intravitreal ranibizumab led to significant improvement in BCVA and a greater reduction in central macular thickness (CMT), with faster resolution of neurosensory detachment compared with placebo (13.0 ± 3.1 vs 4.2 ± 0.9 weeks; P < 0.001). Several studies by Lim et al., Artunay et al., and Chhablani et al. have demonstrated the efficacy of intravitreal bevacizumab in treating CSCR.[52,53,54] The CONTAIN study showed that chronic CSCR patients treated with aflibercept achieved SRF resolution in 50% of cases, though without significant BCVA improvement, suggesting better anatomical than functional outcomes.[55] Maiko Inoue et al.[56] followed patients with chronic CSCR for one year after intravitreal bevacizumab and observed maintained BCVA with decreased serous detachment. Schaal et al.[57] reported anatomical and functional improvement in a series of 12 patients treated with bevacizumab, implying a role for VEGF in fluid leakage and a therapeutic effect of anti-VEGF agents. Conversely, Chung et al.,[58] in a meta-analysis, found no significant BCVA difference at six months between bevacizumab and observation alone. Similarly, Ji et al.[59] analyzed 14 studies (266 eyes) and noted that for acute CSCR, anti-VEGF was not superior to observation in terms of BCVA or CMT at six months. For chronic CSCR, anti-VEGF treatment showed no statistically significant advantage, possibly confounded by the disease’s self-limiting nature. Chhablani et al.[54] found that anti-VEGF agents (bevacizumab, ranibizumab, and aflibercept) were safe and effective as primary therapy for MNV secondary to CSCR, with no major adverse events reported. Anti-VEGF agents have demonstrated promising anatomical benefits in CSCR, particularly when secondary MNV is present. However, functional improvement and complete resolution of SRF remain inconsistent, and high-quality randomized trials are still lacking. At present, anti-VEGF therapy should be considered adjunctive or selectively indicated rather than routine in chronic CSCR management.

B) Choroidal Osteoma

Choroidal osteoma is a rare ossifying tumor of the choroid that predominantly affects young females in the second decade of life. Clinically, it appears as a deep, yellowish–orange lesion at the juxtapapillary or macular region, often showing branching “spider-like” surface vessels. Visual loss may result from gradual retinal atrophy overlying the lesion, accumulation of SRF, or hemorrhage secondary to MNV [Fig. 2].[60] The introduction of anti-VEGF therapy has expanded treatment options for choroidal osteoma, especially when MNV is present. Ahmadieh and Vafi first reported successful regression of CNVM associated with choroidal osteoma following intravitreal bevacizumab injection.[61] Khan et al.[62] later demonstrated anatomical improvement and modest visual gain with serial anti-VEGF injections, either alone or combined with PDT. Najafabadi et al.[63] reported resolution of serous retinal detachment unrelated to CNVM after a single intravitreal bevacizumab injection, suggesting a role for VEGF inhibition even in non-neovascular cases. Similarly, Brody et al. and Cherian et al. described cases where SRF without CNVM responded favorably to aflibercept and bevacizumab, respectively.[64,65] Overall, anti-VEGF agents such as bevacizumab and ranibizumab are effective in reducing SRF and stabilizing or improving visual outcomes in cases of choroidal osteoma with or without MNV, especially when the lesion is juxtafoveal or subfoveal. Anti-VEGF therapy offers a safe and effective treatment option for managing choroidal osteoma complicated by MNV or SRF. It leads to favorable anatomical outcomes and modest visual gains, particularly in juxtafoveal lesions. Further studies are warranted to establish long-term efficacy and optimize treatment intervals.

Figure 2.

(a) Widefield color fundus photo of the left eye showing a lesion with partial scarring with subretinal and intraretinal hemorrhage involving the macula at presentation. (b) Color fundus photo of the left eye showing a lesion with subretinal and intraretinal hemorrhage involving the macula at presentation. (c) Widefield color fundus photo of the left eye showing a lesion with scarring and fibrosis with resolved intraretinal hemorrhage involving the macula after anti-VEGF injection. (d) Color fundus photo of the left eye showing scarred lesion with fibrosis after anti-VEGF injection. VEGF = Vascular endothelial growth factor

C) Inherited Retinal Diseases Associated with Macular Neovascularization

IRDs represent a heterogeneous group of genetic disorders that cause progressive vision loss through photoreceptor and retinal pigment epithelial dysfunction. Complications such as CME, foveoschisis, macular hole, epiretinal membrane, vitelliform lesions, and MNV may further compromise vision.[66]

i) Sorsby Fundus Dystrophy

Sorsby fundus dystrophy is an autosomal dominant macular dystrophy caused by mutations in the TIMP3 gene on chromosome 22q12.3. These mutations reduce metalloproteinase inhibitory activity, increasing VEGF binding and angiogenic signaling. Intravitreal ranibizumab and bevacizumab have been shown to be safe and effective for MNV secondary to Sorsby fundus dystrophy, leading to reduced scarring and stabilized vision even in advanced cases.[67,68,69]

ii) Doyne’s Honeycomb Retinal Dystrophy (Malattia Leventinese)

Mutations in the EFEMP1 gene cause Doyne’s honeycomb retinal dystrophy, characterized by basal laminar deposits, complement activation, and RPE–choroidal dysfunction that predispose to MNV. Anti-VEGF agents can restore retinal architecture and improve visual acuity despite underlying RPE abnormalities.[70,71]

iii) Choroideraemia

Choroideraemia is an X-linked disorder leading to progressive chorioretinal atrophy. Although MNV is rare, isolated case reports have shown favorable visual and anatomical outcomes following intravitreal ranibizumab or bevacizumab in young patients with choroideraemia-related MNV.[72]

iv) Gyrate Atrophy

Gyrate atrophy, caused by deficiency of the vitamin B6–dependent enzyme ornithine ketoacid aminotransferase, may rarely be complicated by subfoveal MNV. Both ranibizumab and bevacizumab have been effective in reducing leakage and improving vision in reported cases.[73,74,75]

v) Retinitis Pigmentosa

CME is a common cause of central vision loss in RP. VEGF levels in RP-associated CME are variable; thus, anti-VEGF therapy shows inconsistent results. Yuzbasioglu et al. reported anatomical and visual improvement with intravitreal bevacizumab in 13 eyes of seven patients, whereas Melo et al. noted no benefit in two patients treated similarly.[76,77] Stacey Strong et al.[78] demonstrated the safety of serial aflibercept injections in 30 patients with RP-related CME, but visual outcomes varied. However, anti-VEGF therapy remains effective for secondary MNV in RP.

Anti-VEGF agents have shown encouraging results in managing MNV associated with various inherited retinal dystrophies, particularly Sorsby fundus dystrophy, Doyne’s honeycomb dystrophy, and choroideraemia. Although the response in RP-related CME is variable, these agents provide a valuable adjunctive option in selected cases. Given the rarity and heterogeneity of IRDs, multicentric studies are needed to validate efficacy and establish optimal treatment protocols.

D) Best Vitelliform Macular Dystrophy

Best vitelliform macular dystrophy is a hereditary form of progressive macular dystrophy caused by a mutation in the BEST1 gene (also known as the VMD2 gene) located on the long arm of chromosome 11q12. It is considered to have the following clinical stages: Stage I (Previtelliform) with subtle RPE changes (tiny, central honeycomb structure centrally), Stage II (Vitelliform) with classic “egg-yolk” lesion, Stage III (Pseudohypopyon) with layering of lipofuscin, Stage IV (Vitelloeruptive) with“scrambled egg” appearance, Stage V (Atrophic) with central RPE and retinal atrophy, and lastly Stage VI which is characterized by formation of CNVM.[79] Khan et al.[80] in their study of 14 eyes reported that best related MNV treated with intravitreal bevacizumab was associated with statistically better visual acuity outcomes (logMAR) than observation alone. Anti-VEGF agents, when given in a PRN regime, helped in the reduction of SRF in such cases.

E) Angioid Streaks

Angioid streaks are characterized by linear, crack-like dehiscences within Bruch’s membrane, resulting from degeneration and mineralization of its elastic and collagenous layers. These changes are often accompanied by secondary atrophy of the RPE and choriocapillaris. The most common and vision-threatening complication is the development of MNV, which occurs in up to 86% of affected patients and typically presents bilaterally with asymmetrical involvement. The most frequent systemic association is pseudoxanthoma elasticum (PXE), though angioid streaks may also occur idiopathically or with systemic conditions such as Paget’s disease and sickle-cell anemia. Visual loss in PXE-related angioid streaks may result from MNV and from progressive outer retinal and RPE atrophy, which can occur independent of neovascularization.[81] Teixeira et al.[82] first reported the successful use of off-label intravitreal bevacizumab for MNV secondary to angioid streaks in 2006. Since then, various anti-VEGF agents, including bevacizumab, ranibizumab, and aflibercept, have been used with favorable results. Miki Sawa et al.[83] demonstrated that long-term bevacizumab therapy led to visual stabilization and quiescence of MNV, although recurrence occurred in nearly half of their cases. Finger et al.[84] similarly reported improvement and sustained stabilization of visual acuity with monthly ranibizumab injections. Overall, anti-VEGF therapy has become the mainstay for treating MNV secondary to angioid streaks, producing visual and anatomical improvement comparable to that seen in ARMD. Nevertheless, recurrence remains common, necessitating continued surveillance and retreatment as required. Anti-VEGF agents provide significant visual and anatomical benefits in managing MNV secondary to angioid streaks and remain the treatment of choice. However, recurrent neovascular activity is frequent, and most patients require long-term follow-up and repeated injections for sustained disease control.

F) Tubercular Granuloma

Tubercular granulomas are hypoxic granulomatous manifestations of intraocular tuberculosis with increased expression of VEGF. The mainstay of management includes a combination of antitubercular therapy (ATT) and oral corticosteroids. Babu et al.[85] and Jain et al.[86] used anti-VEGF therapy to treat vascularized choroidal tubercular granuloma, wherein intravitreal bevacizumab was used as an adjunct therapy and showed great improvements. Bansal et al.[87] gave a therapeutic trial with intravitreal bevacizumab (1.25 mg in 0.05 mL) injections as an adjunct to ATT and corticosteroids in a 43-year-old woman with a tubercular choroidal granuloma, which resulted in prompt regression of the granuloma and restoration of visual acuity. Similarly, Manisha Agarwal et al.[88] in their study showed the quantitative decrease in the intraocular VEGF levels, which corresponded to the clinical regression of the granulomas with SRF resolution after intravitreal anti-VEGF injections. They emphasized the need for more frequent administration of intravitreal anti-VEGF injections due to a much higher VEGF load in tubercular granulomas as compared to treating CNVMs. Anti-VEGF therapy acts as an adjunct to conventional ATT and corticosteroids in treating the highly vascularized choroidal tubercular granulomas.

Conclusion

The expanding use of anti-VEGF therapy beyond conventional indications such as ARMD, diabetic retinopathy, and RVO has redefined the management of several retinal disorders. Evidence across entities, including CSCR, MacTel, Coats’ disease, choroidal osteoma, angioid streaks, retinal vascular tumors, and selected inherited dystrophies, demonstrates that anti-VEGF agents can achieve significant anatomical improvement and, in many cases, functional visual gains. Nonetheless, outcomes remain heterogeneous due to variable disease mechanisms, limited sample sizes, and the absence of large randomized trials. Anti-VEGF therapy should therefore be regarded as a targeted adjunctive strategy, applied judiciously in well-selected cases. Future research focusing on optimized dosing, long-term safety, and combination protocols will further refine its role in the management of these uncommon yet clinically significant retinal disorders.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.