Etiological Factors and Visual Outcomes of Dense Vitreous Hemorrhage in Patients Aged 80 years and above over the Past Decade in a Tertiary General Hospital

This study aimed to investigate the main etiological factors and visual outcomes in patients with dense vitreous hemorrhage (DVH) aged ≥80 years. We retrospectively included patients with DVH aged ≥80 years who were admitted to our ophthalmology department between January 1, 2010, and December 31, 2019. All patients underwent pars plana vitrectomy (PPV). Data regarding demographic characteristics; preoperative and postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP), and ophthalmic B-scan ultrasonography findings; intraoperative conditions; and postoperative complications were collected and analyzed. A total of 44 patients (44 eyes) were enrolled, with a median age of 82 years; among them, 25 patients (56.82%) were men. The median preoperative BCVA was 2.3 (1.1–3.0). The main etiological factors included retinal vein occlusion (RVO) (20 eyes, 45.45%), polypoidal choroidal vasculopathy (PCV) (15 eyes, 34.09%), proliferative diabetic retinopathy (PDR) (7 eyes, 15.90%), retinal arterial macroaneurysm (RAM) (1 eye, 2.27%), and posterior vitreous detachment (PVD) (1 eye, 2.27%). The median final BCVA was 1.92 (0.5–2.6). There was a significant postoperative improvement in the BCVA; moreover, branch RVO (BRVO) had a better postoperative visual prognosis than central RVO (CRVO), PCV, and PDR (P < 0.05). The final postoperative BCVA was significantly better when the initial BCVA was above hand motion (HM) than when it was HM or lower (P < 0.05). Our findings indicate that RVO, PCV, and PDR were the main causes of DVH. Microinvasive PPV is a safe and effective method that can clarify diagnosis and improve BCVA. Patients with BRVO and preoperative BCVA > HM may have a relatively good visual prognosis. For patients aged ≥80 years who have an appropriate general condition, PPV can be timely performed to treat DVH.


Introduction
Population aging is a global problem.Worldwide, the proportion of people aged ≥65 years is expected to increase from 6.9% in 2000 to 16.4% in 2050, while the proportion of very elderly individuals is expected to increase from 1.9% to 4.2% [1].Although the very elderly population accounts for a small proportion of the human population, it comprises a signifcant proportion of ophthalmic patients.
Vitreous hemorrhage (VH) is among the most common ocular diseases and is known to cause vision loss.Dense VH (DVH) in patients aged ≥80 years seriously afects vision, which increases the risk of falling and fracture, and thus increases the burden on the family and afects the survival rate [2,3].Accordingly, DVH is an increasingly concerning problem among patients aged ≥80 years.
In clinical settings, identifying the cause of DVH is often challenging because the fundus is not easily visible.Furthermore, the clinical causes of DVH may difer between older and younger patients.In addition, the characteristics and prognosis of DVH in elderly patients with DVH, especially those aged ≥80 years, remain unclear.Terefore, this study aimed to investigate the main etiological factors and visual outcomes of DVH in patients aged ≥80 years.

Study Participants.
We retrospectively reviewed the electronic medical records of patients with DVH aged ≥80 years who were admitted to the Department of Ophthalmology, Jiangsu Province Hospital, between January 1, 2010, and December 31, 2019.Tis study adhered to the tenets of the Declaration of Helsinki.Furthermore, this study was approved by the Ethics Committee of Jiangsu Province Hospital.
Te diagnostic criteria for DVH were as follows: (1) bestcorrected visual acuity (BCVA) ≤0.1; (2) severe VH, which was too dense to allow visualization of the posterior pole of the retina; and (3) B-scan ultrasound showing no signs of retinal tear or retinal detachment (RD).Te exclusion criteria were as follows: a history of VH due to retinal vein occlusion (RVO), posterior vitreous detachment (PVD), recent trauma, Terson's syndrome, and so on, which had been absorbed without intervention when they were younger than 80 years old; had a history of glaucoma; having previously undergone pars plana vitrectomy (PPV); a diagnosis of advanced dementia; and a follow-up period of <6 months.
We collected demographic data including age and sex.Te data regarding clinical characteristics, including intraoperative fndings; complications; and follow-up duration, were also collected.Te patients were examined before surgery as well as 1 day; 1 week; and 1, 3, and 6 months after surgery.Te patients underwent comprehensive ophthalmic examinations, including BCVA measurement (E standard logarithmic visual acuity chart), intraocular pressure (IOP) measurement, slit-lamp dilated biomicroscopy, and indirect ophthalmoscopy.Optical coherence tomography (OCT), fundus fuorescein angiography (FFA), and indocyanine angiography (ICGA) were performed postoperatively in some patients.
2.2.Surgical Procedure.All surgeries were performed by experienced vitreoretinal specialists.After retrobulbar block using a 4 ml mixture of 0.75% bupivacaine and 2% lidocaine in a 1 : 1 ratio, a standard three-port 23-gauge, or 25-gauge vitrectomy with a wide-angle, noncontact viewing system (Resight ® ; Carl Zeiss Meditec AG, Jena, Germany) was performed using the constellation vision system (Alcon Laboratories Inc., Fort Worth, TX, USA).For phakic eyes, combined surgery involving phacoemulsifcation and intraocular lens implantation was performed using the same machine before vitrectomy.During vitrectomy, thick vitreous blood around the vitreous cutting head and optical fber was initially removed.Subsequently, the anterior and posterior vitreous cavities were removed.If necessary, triamcinolone acetonide was injected to mark the residual vitreous cortex.Using assisted scleral indentation, clear and meticulous shaving of the vitreous base was performed using a wide-angle viewing system.Next, the organized vitreoretinal bands as well as proliferative and neovascular membranes were carefully separated and resected.Hemostasis was achieved by raising the IOP or using endodiathermy.Laser photocoagulation was performed for ischemic areas or holes.At the end of surgery, a balanced salt solution, air, or silicone oil was used to fll the vitreous cavity, as appropriate.
Te patients were divided into four groups according to the four main causes.Tere was no signifcant among-group diference in postoperative BCVA (Table 3).However, the BRVO group had signifcantly better postoperative visual prognosis than the other three groups (Table 4).
In addition, patients were divided into two groups based on the initial BCVA as follows: group A, BCVA ≤ HM, and group B, BCVA > HM.Group B showed a signifcantly better fnal postoperative BCVA than group A (Table 5).
Te IOP of all patients was within the normal range before and after surgery.No serious complications such as suprachoroidal hemorrhage or recurrent RD occurred.

Discussion
VH occurs secondary to various ocular or systemic diseases.A small amount of vitreous blood can be absorbed without intervention; however, vitreous blood in VH is difcult to absorb, which seriously afects the patient's vision and 2 Journal of Ophthalmology impedes diagnosis by ophthalmologists.Specifcally, extensive unabsorbed vitreous blood may cause proliferative reactions in the vitreous, form abnormal neovascular fbrous proliferative membranes, and cause massive hemorrhage.Furthermore, the proliferative membrane can pull the retina to form holes or even lead to RD. Terefore, we routinely perform PPV to treat DVH and to clarify its etiological factors.PDR, retinal vasculitis, and BRVO have been reported as the major causes of VH in adults [5,6].Given the unique physiological characteristics of the very elderly population, they may have diferent etiological factors of DVH.
However, the specifc characteristics and prognosis of very elderly patients with DVH, particularly those aged ≥80 years, remain unclear.We found that the most common etiologies in these patients were RVO, PCV, and PDR, which is inconsistent with previous reports [5,6].Te disease spectrum and treatment strategies of the elderly group over 80 years old are diferent from those of middle-aged people.Te elderly population is a vulnerable group and often even gives up treatment without intervention.Terefore, we aimed to investigate the causes of vitreous hemorrhage in elderly patients over 80 years old and whether treatment is meaningful.
In our study, the main cause of DVH in patients aged ≥80 years was RVO.DVH is a severe advanced complication of RVO, which is caused by dilation of obstructed blood vessels and rupture of retinal neovascularization.Hypertension is the strongest systemic risk factor for RVO [7].Since the central retinal veins and arteries are located in the same adventitial sheath within the lamina cribrosa, arterial stifness may afect the adjacent veins, resulting in CRVO [8].BRVO may result from vein compression at arteriovenous crossings, degenerative changes within the venous walls, and hypercoagulability [8].Systolic blood pressure is positively correlated with age, which could be the main factor for the increase in the incidence and prevalence of hypertension with age [9].
Te second most common cause of DVH in our study was PCV.PCV is characterized by persistent, recurrent serous leakage, and hemorrhage in the macula in elderly individuals, which is caused by a peculiar form of choroidal neovascularization in the inner choroid [10].Characteristic abnormalities observed in PCV include a branching vascular network and polypoidal structures at the lesion boundary.Asian ethnicity is associated with the risk of developing PCV [11,12].Tsujikawa et al. reported that a relatively large PCV (lesion area ≥1 optic disc area) was associated with an increased risk of extensive subretinal hemorrhage [13], which is more likely to cause dense breakthrough VH [14].Patients with PCV and hypertension, diabetes, and cardiovascular disease have an increased risk of recurrent subretinal bleeding; moreover, these systemic diseases are very common in the very elderly population.Compared with classic age-related macular degeneration, hemorrhagic type PCV presents as hemorrhagic pigment epithelial detachment, with more subretinal hemorrhage in the macula and more frequent occurrence of explosive severe vitreous hemorrhage, resulting in a sudden decrease in the patient's vision.Furthermore, the limited number of enrolled patients was also an infuencing factor.Tus, in this study, classic agerelated macular degeneration patients were not collected.
Te third most common cause of DVH in our study was PDR.PDR results from retinal ischemia and is characterized by the growth of new blood vessels on the surface of the retina or optic disc.Tese abnormal vessels may lead to VH, subsequent fbrosis, and tractional RD.Te incidence of diabetic retinopathy (DR) increases with age and clinical progression of diabetes [15].However, at the individual level, diabetes causes greater life loss and has a higher premature death index than hypertension [16].G, group.* : G1 vs. G2: 0.047; G2 vs. G3: 1.000; G1 vs. G3: 0.001; G3 vs. G4: 1.000; G2 vs. G4: 1.000; G1 vs. G4: 0.010.We observed a signifcant postoperative improvement in BCV (P < 0.05).Notably, one patient with PCV showed vision improvement in the early postoperative period; however, she sufered from retinal rehemorrhage and her vision eventually deteriorated.Te patient refused further treatment with antivascular endothelial growth factor (anti-VEGF).Among the remaining patients, the BCVA improved and remained unchanged in 40 and 3 patients, respectively.PPV can clear cloudy vitreous and infammatory factors in the vitreous body to facilitate identifcation of the conditions of the retina and choroid.Laser treatment was administered intraoperatively as supplementary treatment, if necessary.
Among the etiologies, BRVO had a better postoperative visual prognosis than the other three etiologies (P < 0.05).
Te visual prognosis of RVO is related to retinal blood supply, macular edema, and optic nerve conditions.Compared with BRVO, CRVO involved worse visual prognosis, which could be primarily attributed to widespread ischemic retinal damage, severe macular edema, or glaucomatous optic nerve damage.
Submacular hemorrhage is a serious complication of PCV that can lead to severe and irreversible damage to the photoreceptors and outer nuclear layer [17].In the PCV group, all patients had submacular hemorrhage and, as a result, had a poor visual prognosis.Other common macular manifestations of severe PCV are associated with poor BCVA.For example, persistent macular serous RD causes the degeneration and atrophy of the macular retinal pigmentary epithelium; moreover, subretinal fbrovascular proliferation seriously impairs macular function [18].However, most patients with PCV describe subjective improvement due to an improved visual feld.
In our study, the PDR group had a worse visual prognosis than the BRVO group.Elderly patients with diabetes and DVH usually have poor control of blood sugar and blood pressure.Te poor visual prognosis in this subgroup could be attributed to chronic high glucose levels and ischemia in the retina and optic nerve.
In our study, we found that the fnal postoperative BCVA was signifcantly better when the initial BCVA was above the HM than when the BCVA was HM or lower (P < 0.05).Tis indicates that preoperative visual function is positively correlated with the postoperative visual prognosis.
Tis study has several strengths.First, the data were collected from a tertiary general hospital.Compared with specialized hospitals, general hospitals have stronger comprehensive medical strength and a larger geriatric ward; moreover, they have more elderly patients, which is conducive to this study.Second, the observation period (10 years) allowed extensive collection of useful information.Moreover, within the past 10 years, there has been rapid development of minimally invasive PPV technology; accordingly, more patients aged ≥80 years with DVH may have had the opportunity for surgery.Terefore, the results of this study are representative.
However, this study had several limitations.First, given the recent reforms to China's medical insurance system, an increasing number of patients can aford antiVEGF treatment.However, among our patients, few patients could aford multiple anti-VEGF treatments owing to high costs.Second, as a new technology, intravitreal injection of a recombinant tissue plasminogen activator has been used to treat patients with PCV who develop extensive macular hemorrhage at an early stage, which can reduce the toxic efect of blood on the retinal pigmentary epithelium and photoreceptors [19].Although these interventions can improve the vision and prognosis of patients, they were not administered to our patients.Tird, the present study is a retrospective design.

Conclusions
In conclusion, RVO, PCV, and PDR are the main causes of DVH in patients aged ≥80 years.Microinvasive PPV is a safe and efective method for facilitating diagnosis and improving VA.Patients with BRVO and preoperative BCVA > HM may have a relatively good visual prognosis.For patients aged ≥80 years who have an appropriate general condition, PPV can be timely performed to treat DVH.

Table 3 :
Comparison of preoperative BCVA among the four major etiological groups.

Table 4 :
Comparison of postoperative BCVA among the four major etiological groups.

Table 5 :
Comparison of the fnal BCVA between the two groups with diferent initial BCVAs.
G: group; N: number of eyes.

Table 1 :
Etiology of DVH in patients aged ≥80 years.