The results of the present study show lower surgical success, higher IOP, and more glaucoma medications in patients experiencing HP after AGV implantation. Besides, the observed difference remained in the long-term period of 5 years, which is shown for the first time to the best of our knowledge.
Our results are in line with those of the previous reports investigating the effect of HP on the IOP outcome. Nouri-Mahdavi and Caprioli found a higher mean IOP and more required glaucoma medications by passing 6 to 12 months from surgery in eyes with an HP. Similarly, Jung  reported higher IOP in the HP group compared to the non-HP group after 1 year, while the difference in surgical success did not reach a significant level. Subsequently, Jeong et al. reported lower IOP control and worse success in eyes with HP after 2 years from the operation. Our study with a longer duration of follow-up has also shown a lower rate of success in the HP group.
Similar to Nouri-Mahdavi et Caprioli’s study, we considered the IOP more than 21 mm Hg after 3 months, as a surgical failure, rather than an HP. Although the exact mechanism underlying HP has not been exactly clarified yet, various mechanisms have been proposed in this regard. The most plausible explanation relates the HP to the normal wound healing process, consequent fibrosis formation, and bleb encapsulation. The histopathological studies investigating the wound healing process after GDD implantation reported a difference between the staged processes and procedures in which the aqueous flow is immediately established like AGV. The mechanical pressure of the aqueous or the pro-inflammatory cytokines present in AC was hypothetically indicated to result in a full-thickness thick bleb wall around the plate.
The HP usually peaks after one month, which accords to the timing of fibrosis formation around the AGV plate. In contrast, Jung et al. using anterior segment optical coherence tomography demonstrated thinner wall of the bleb accordant with the timing of HP and then postulated the collagen cross-linking as the mechanism underlying the pathophysiology of thinner bleb and HP. Moreover, the HP was not resolved in approximately two-third of the included patients. Besides, all HP patients needed glaucoma medication in the first year.
Moreover, there is a potential role for steroids as an inducer of high IOP after the surgery. Correspondingly, Yuen et al. reported lower HP rates in patients receiving nonsteroidal inflammatory drugs (NSAID), as a substitute for the topical steroid. Besides, the inflammatory cytokine level was found to be correlated with higher IOP in the glaucomatous eyes with an HP. However, it still seems unclear whether these cytokines are stimulated with high IOP or they are contributing to the development of the HP. Intrinsic characteristics of the implanted device might also play a role in the HP since the HP more frequently occurs after AGV implantation compared to Baerveldt[11, 21] or Molteno devices. The valved nature of the AGV and lower surface area has been proposed as the possible cause of a higher prevalence of HP after AGV implantation.
In this study, we estimated the prevalence of HP lower than the reports in the literature. The incidence of HP widely differs among different studies. The earlier studies reported higher prevalence rates (56%  and 82%), while more recent studies estimated lower prevalence rates (31 %[7, 9]). Because of the worse outcome after HP, multiple methods were proposed to prevent the HP including intraoperative and postoperative triamcinolone or antimetabolite injection, early start of glaucoma medications, and medical suppression of aqueous humor soon after the surgery. Pakravan et al. reported the HP difference as 66.0 % and 23.4 % (P < 0.001%) in groups with the early start of fixed dorzolamide and timolol, respectively. In another study, intraoperative sub-tenon Triamcinolone injection resulted in the HP difference between the two study groups. (26 % vs 52%, P = 0.027 respectively). The use of Ketorolac in comparison to steroid eye drops has also led to lower HP occurrence ( 31% vs 53 %, P = 0.27)19. However, we did not apply the specific proposed methods for the prevention of the hypertensive phase. The IOP lowering medications were started either when the IOP passed the target pressure or when there was a pattern of the continuous rising of IOP between follow-up visits.
Another interesting result of the present study is the worse outcome in the group experiencing early HP compared with the group of late-onset HP. Since the difference did not reach a statistically significant level, making a clear conclusion is not possible. However, in our experience, it was shown that HP entails a heterogeneous group of patients with different outcomes. Furthermore, Cheng et al. investigated the opening and closing pressures in the AGVs and then hypothesized that high opening pressure (cutoff of 18 mm Hg) and low closing pressure (cutoff less than 7 mm Hg) were both related to the early hypertensive phase, while they did not affect the late HP. Therefore, we assume that there may be some tube-related factors affecting early HP that remain for a longer duration compared to late HP and consequently result in a worse outcome.
Several factors were reported in different studies as the risk factors for the HP development, including higher baseline IOP and long axial length. In the present study, the only factor found to be associated with HP development was the presence of neovascular glaucoma. Also, it was indicated that more prevalent inflammatory cytokines in the aqueous of the patients with NVG result in the more prominent fibrovascular reaction, so they might be the underlying mechanisms. In contrast to the previous reports, higher baseline IOP was not a factor affecting HP development, while it could predict the long-term success in a Cox proportional hazard regression model.
Our limitations are also included, but they are not limited to the retrospective nature of the study, small sample size, and different types of glaucoma.
In conclusion, we reported worse IOP outcomes, higher needs to glaucoma medications, and lower success rates in patients who experienced a hypertensive phase in the 5 years postoperatively. Patients experiencing HP in the earlier period after the surgery might also have a worse outcome compared to the patients experiencing HP for a period of 1.5 to 3 months after the procedure. In this regard, larger studies are required to investigate the possible difference between two groups of HP.